title: Medroxyprogesterone acetate

text: When combined with CEEs, MPA has been associated with an increased risk of breast cancer, dementia, and thrombus in the eye. In combination with estrogens in general, MPA may increase the risk of cardiovascular disease, with a stronger association when used by postmenopausal women also taking CEEs. It was because of these unexpected interactions that the Women's Health Initiative study was ended early due to the extra risks of menopausal hormone therapy, resulting in a dramatic decrease in both new and renewal prescriptions for hormone therapy.


title: Medroxyprogesterone acetate

text: Long-term studies of users of DMPA have found slight or no increased overall risk of breast cancer. However, the study population did show a slightly increased risk of breast cancer in recent users (DMPA use in the last four years) under age 35, similar to that seen with the use of combined oral contraceptive pills.


title: Medroxyprogesterone acetate

text: DMPA has been associated in multiple studies with a higher risk of venous thromboembolism (VTE) when used as a form of progestogen-only birth control in premenopausal women. The increase in incidence of VTE ranges from 2.2-fold to 3.6-fold. Elevated risk of VTE with DMPA is unexpected, as DMPA has little or no effect on coagulation and fibrinolytic factors, and progestogens by themselves normally do not increase the risk of thrombosis. It has been argued that the higher incidence with DMPA has reflected preferential prescription of DMPA to women considered to be at an increased risk of VTE. Alternatively, it is possible that MPA may be an exception among progestins in terms of VTE risk. A 2018 meta-analysis reported that MPA was associated with a 2.8-fold higher risk of VTE than other progestins. It is possible that the glucocorticoid activity of MPA may increase the risk of VTE.


title: Medroxyprogesterone acetate

text: DMPA may cause reduced bone density in premenopausal women and in men when used without an estrogen, particularly at high doses, though this appears to be reversible to a normal level even after years of use.


title: Medroxyprogesterone acetate

text: On 17 November 2004, the United States Food and Drug Administration put a black box warning on the label, indicating that there were potential adverse effects of loss of bone mineral density. While it causes temporary bone loss, most women fully regain their bone density after discontinuing use. The World Health Organization (WHO) recommends that the use not be restricted. The American College of Obstetricians and Gynecologists notes that the potential adverse effects on BMD be balanced against the known negative effects of unintended pregnancy using other birth control methods or no method, particularly among adolescents.


title: Medroxyprogesterone acetate

text: Three studies have suggested that bone loss is reversible after the discontinuation of DMPA. Other studies have suggested that the effect of DMPA use on postmenopausal bone density is minimal, perhaps because DMPA users experience less bone loss at menopause. Use after peak bone mass is associated with increased bone turnover but no decrease in bone mineral density.


title: Medroxyprogesterone acetate

text: The FDA recommends that DMPA not be used for longer than two years, unless there is no viable alternative method of contraception, due to concerns over bone loss. However, a 2008 Committee Opinion from the American Congress of Obstetricians and Gynecologists (ACOG) advises healthcare providers that concerns about bone mineral density loss should neither prevent the prescription of or continuation of DMPA beyond two years of use.


title: Medroxyprogesterone acetate

text: There is uncertainty regarding the risk of HIV acquisition among DMPA users; some observational studies suggest an increased risk of HIV acquisition among women using DMPA, while others do not. The World Health Organization issued statements in February 2012 and July 2014 saying the data did not warrant changing their recommendation of no restriction – Medical Eligibility for Contraception (MEC) category 1 – on the use of DMPA in women at high risk for HIV. Two meta-analyses of observational studies in sub-Saharan Africa were published in January 2015. They found a 1.4- to 1.5-fold increase risk of HIV acquisition for DMPA users relative to no hormonal contraceptive use. In January 2015, the Faculty of Sexual & Reproductive Healthcare of the Royal College of Obstetricians and Gynaecologists issued a statement reaffirming that there is no reason to advise against use of DMPA in the United Kingdom even for women at 'high risk' of HIV infection. A systematic review and meta-analysis of risk of HIV infection in DMPA users published in fall of 2015 stated that "the epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission." In 2019, a randomized controlled trial found no significant association between DMPA use and HIV.


title: Medroxyprogesterone acetate

text: MPA may be used by breastfeeding mothers. Heavy bleeding is possible if given in the immediate postpartum time and is best delayed until six weeks after birth. It may be used within five days if not breast feeding. While a study showed "no significant difference in birth weights or incidence of birth defects" and "no significant alternation of immunity to infectious disease caused by breast milk containing DMPA", a subgroup of babies whose mothers started DMPA at two days postpartum had a 75% higher incidence of doctor visits for infectious diseases during their first year of life.


title: Medroxyprogesterone acetate

text: A larger study with longer follow-up concluded that "use of DMPA during pregnancy or breastfeeding does not adversely affect the long-term growth and development of children". This study also noted that "children with DMPA exposure during pregnancy and lactation had an increased risk of suboptimal growth in height," but that "after adjustment for socioeconomic factors by multiple logistic regression, there was no increased risk of impaired growth among the DMPA-exposed children." The study also noted that effects of DMPA exposure on puberty require further study, as so few children over the age of 10 were observed.


title: Medroxyprogesterone acetate

text: MPA has been studied at "massive" dosages of up to 5,000 mg per day orally and 2,000 mg per day via intramuscular injection, without major tolerability or safety issues described. Overdose is not described in the Food and Drug Administration (FDA) product labels for injected MPA (Depo-Provera or Depo-SubQ Provera 104). In the FDA product label for oral MPA (Provera), it is stated that overdose of an estrogen and progestin may cause nausea and vomiting, breast tenderness, dizziness, abdominal pain, drowsiness, fatigue, and withdrawal bleeding. According to the label, treatment of overdose should consist of discontinuation of MPA therapy and symptomatic care.


title: Medroxyprogesterone acetate

text: MPA increases the risk of breast cancer, dementia, and thrombus when used in combination with CEEs to treat menopausal symptoms. When used as a contraceptive, MPA does not generally interact with other medications. The combination of MPA with aminoglutethimide to treat metastases from breast cancer has been associated with an increase in depression. St John's wort may decrease the effectiveness of MPA as a contraceptive due to acceleration of its metabolism.


title: Medroxyprogesterone acetate

text: MPA acts as an agonist of the progesterone, androgen, and glucocorticoid receptors (PR, AR, and GR, respectively), activating these receptors with EC values of approximately 0.01 nM, 1 nM, and 10 nM, respectively. It has negligible affinity for the estrogen receptor. The medication has relatively high affinity for the mineralocorticoid receptor, but in spite of this, it has no mineralocorticoid or antimineralocorticoid activity. The intrinsic activities of MPA in activating the PR and the AR have been reported to be at least equivalent to those of progesterone and dihydrotestosterone (DHT), respectively, indicating that it is a full agonist of these receptors.


title: Medroxyprogesterone acetate

text: MPA is a potent agonist of the progesterone receptor with similar affinity and efficacy relative to progesterone. While both MPA and its deacetylated analogue medroxyprogesterone bind to and agonize the PR, MPA has approximately 100-fold higher binding affinity and transactivation potency in comparison. As such, unlike MPA, medroxyprogesterone is not used clinically, though it has seen some use in veterinary medicine. The oral dosage of MPA required to inhibit ovulation (i.e., the effective contraceptive dosage) is 10 mg/day, whereas 5 mg/day was not sufficient to inhibit ovulation in all women. In accordance, the dosage of MPA used in oral contraceptives in the past was 10 mg per tablet. For comparison to MPA, the dosage of progesterone required to inhibit ovulation is 300 mg/day, whereas that of the 19-nortestosterone derivatives norethisterone and norethisterone acetate is only 0.4 to 0.5 mg/day.


title: Medroxyprogesterone acetate

text: The mechanism of action of progestogen-only contraceptives like DMPA depends on the progestogen activity and dose. High-dose progestogen-only contraceptives, such as DMPA, inhibit follicular development and prevent ovulation as their primary mechanism of action. The progestogen decreases the pulse frequency of gonadotropin-releasing hormone (GnRH) release by the hypothalamus, which decreases the release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) by the anterior pituitary. Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels. Progestogen negative feedback and the lack of estrogen positive feedback on LH release prevent a LH surge. Inhibition of follicular development and the absence of a LH surge prevent ovulation. A secondary mechanism of action of all progestogen-containing contraceptives is inhibition of sperm penetration by changes in the cervical mucus. Inhibition of ovarian function during DMPA use causes the endometrium to become thin and atrophic. These changes in the endometrium could, theoretically, prevent implantation. However, because DMPA is highly effective in inhibiting ovulation and sperm penetration, the possibility of fertilization is negligible. No available data support prevention of implantation as a mechanism of action of DMPA.


title: Medroxyprogesterone acetate

text: MPA suppresses the hypothalamic–pituitary–adrenal (HPA) and hypothalamic–pituitary–gonadal (HPG) axes at sufficient dosages, resulting decreased levels of gonadotropins, androgens, estrogens, adrenocorticotropic hormone (ACTH), and cortisol, as well as levels of sex hormone-binding globulin (SHBG). There is evidence that the suppressive effects of MPA on the HPG axis are mediated by activation of both the PR and the AR in the pituitary gland. Due to its effects on androgen levels, MPA can produce strong functional antiandrogenic effects, and is used in the treatment of androgen-dependent conditions such as precocious puberty in boys and hypersexuality in men. In addition, since the medication suppresses estrogen levels as well, MPA can produce strong functional antiestrogenic effects similarly, and has been used to treat estrogen-dependent conditions such as precocious puberty in girls and endometriosis in women. Due to low estrogen levels, the use of MPA without an estrogen poses a risk of decreased bone mineral density and other symptoms of estrogen deficiency.


title: Medroxyprogesterone acetate

text: Oral MPA has been found to suppress testosterone levels in men by about 30% (from 831 ng/dL to 585 ng/dL) at a dosage of 20 mg/day, by about 45 to 75% (average 60%; to 150–400 ng/dL) at a dosage of 60 mg/day, and by about 70 to 75% (from 832–862 ng/dL to 214–251 ng/dL) at a dosage of 100 mg/day. Dosages of oral MPA of 2.5 to 30 mg/day in combination with estrogens have been used to help suppress testosterone levels in transgender women. One study of injectable MPA in men with benign prostatic hyperplasia reported that a single 150 mg dose suppressed testosterone levels into the defined male castrate range (<58 ng/dL) within 7 days and that castration levels of testosterone were maintained for 3 months. Very high doses of intramuscular MPA of 150 to 500 mg per week (but up to 900 mg per week) have similarly been reported to suppress testosterone levels to less than 100 ng/dL. The typical initial dose of intramuscular MPA for testosterone suppression in men with paraphilias is 400 or 500 mg per week.


title: Medroxyprogesterone acetate

text: MPA is a potent full agonist of the AR. Its activation of the AR may play an important and major role in its antigonadotropic effects and in its beneficial effects against breast cancer. However, although MPA may produce androgenic side effects such as acne and hirsutism in some women. In fact, likely due to its suppressive actions on androgen levels, it has been reported that MPA is generally highly effective in improving pre-existing symptoms of hirsutism in women with the condition. However, MPA has been seen to cause androgenic effects in children with precocious puberty. The reason for the general lack of virilizing effects with MPA, despite it binding to and activating the AR with high affinity and this action potentially playing an important role in many of its physiological and therapeutic effects, is not entirely clear. However, MPA has been found to interact with the AR differently compared to other agonists of the receptor such as dihydrotestosterone (DHT). The result of this difference appears to be that MPA binds to the AR with a similar affinity and intrinsic activity to that of DHT, but requires about 100-fold higher concentrations for a comparable induction of gene transcription, while at the same time not antagonizing the transcriptional activity of normal androgens like DHT at any concentration. Thus, this may explain the low propensity of MPA for producing androgenic side effects.


title: Medroxyprogesterone acetate

text: MPA shows weak androgenic effects on liver protein synthesis, similarly to other weakly androgenic progestins like megestrol acetate and 19-nortestosterone derivatives. While it does not antagonize estrogen-induced increases in levels of triglycerides and HDL cholesterol, DMPA every other week may decrease levels of HDL cholesterol. In addition, MPA has been found to suppress sex hormone-binding globulin (SHBG) production by the liver. At a dosage of 10 mg/day oral MPA, it has been found to decrease circulating SHBG levels by 14 to 18% in women taking 4 mg/day oral estradiol valerate. Conversely, in a study that combined 2.5 mg/day oral MPA with various oral estrogens, no influence of MPA on estrogen-induced increases in SHBG levels was discerned. In another, higher-dose study, SHBG levels were lower by 59% in a group of women treated with 50 mg/day oral MPA alone relative to an untreated control group of women. In massive-dose studies of oral or injectable MPA (e.g., 500–1,000 mg/day), the medication decreased SHBG levels by about 80%.


title: Medroxyprogesterone acetate

text: Unlike the related steroids megestrol acetate and cyproterone acetate, MPA is not an antagonist of the AR and does not have direct antiandrogenic activity. As such, although MPA is sometimes described as an antiandrogen, it is not a "true" antiandrogen (i.e., AR antagonist).


title: Medroxyprogesterone acetate

text: As an agonist of the GR, MPA has glucocorticoid activity, and as a result can cause symptoms of Cushing's syndrome, steroid diabetes, and adrenal insufficiency at sufficiently high doses. It has been suggested that the glucocorticoid activity of MPA may contribute to bone loss. The glucocorticoid activity of MPA may also result in an upregulation of the thrombin receptor in blood vessel walls, which may contribute to procoagulant effects of MPA and risk of venous thromboembolism and atherosclerosis. The relative glucocorticoid activity of MPA is among the highest of the clinically used progestins.


title: Medroxyprogesterone acetate

text: MPA has been found to act as a competitive inhibitor of rat 3α-hydroxysteroid dehydrogenase (3α-HSD). This enzyme is essential for the transformation of progesterone, deoxycorticosterone, and DHT into inhibitory neurosteroids such as allopregnanolone, , and 3α-androstanediol, respectively. MPA has been described as very potent in its inhibition of rat 3α-HSD, with an IC of 0.2 μM and a K (in rat testicular homogenates) of 0.42 μM. However, inhibition of 3α-HSD by MPA does not appear to have been confirmed using human proteins yet, and the concentrations required with rat proteins are far above typical human therapeutic concentrations.


title: Medroxyprogesterone acetate

text: MPA has been identified as a competitive inhibitor of human 3β-hydroxysteroid dehydrogenase/Δ isomerase II (3β-HSD II). This enzyme is essential for the biosynthesis of sex steroids and corticosteroids. The K of MPA for inhibition of 3β-HSD II is 3.0 μM, and this concentration is reportedly near the circulating levels of the medication that are achieved by very high therapeutic dosages of MPA of 5 to 20 mg/kg/day (dosages of 300 to 1,200 mg/day for a 60 kg (132 lb) person). Aside from 3β-HSD II, other human steroidogenic enzymes, including cholesterol side-chain cleavage enzyme (P450scc/CYP11A1) and 17α-hydroxylase/17,20-lyase (CYP17A1), were not found to be inhibited by MPA. MPA has been found to be effective in the treatment of gonadotropin-independent precocious puberty and in breast cancer in postmenopausal women at high dosages, and inhibition of 3β-HSD II could be responsible for its effectiveness in these conditions.


title: Medroxyprogesterone acetate

text: Progesterone, via transformation into neurosteroids such as 5α-dihydroprogesterone, 5β-dihydroprogesterone, allopregnanolone, and pregnanolone (catalyzed by the enzymes 5α- and 5β-reductase and 3α- and 3β-HSD), is a positive allosteric modulator of the GABA receptor, and is associated with a variety of effects mediated by this property including dizziness, sedation, hypnotic states, mood changes, anxiolysis, and cognitive/memory impairment, as well as effectiveness as an anticonvulsant in the treatment of catamenial epilepsy. It has also been found to produce anesthesia via this action in animals when administered at sufficiently high dosages. MPA was found to significantly reduce seizure incidence when added to existing anticonvulsant regimens in 11 of 14 women with uncontrolled epilepsy, and has also been reported to induce anesthesia in animals, raising the possibility that it might modulate the GABA receptor similarly to progesterone.


title: Medroxyprogesterone acetate

text: MPA shares some of the same metabolic routes of progesterone and, analogously, can be transformed into metabolites such as 5α-dihydro-MPA (DHMPA) and 3α,5α-tetrahydro-MPA (THMPA). However, unlike the reduced metabolites of progesterone, DHMPA and THMPA have been found not to modulate the GABA receptor. Conversely, unlike progesterone, MPA itself actually modulates the GABA receptor, although notably not at the neurosteroid binding site. However, rather than act as a potentiator of the receptor, MPA appears to act as a negative allosteric modulator. Whereas the reduced metabolites of progesterone enhance binding of the benzodiazepine flunitrazepam to the GABA receptor "in vitro", MPA can partially inhibit the binding of flunitrazepam by up to 40% with half-maximal inhibition at 1 μM. However, the concentrations of MPA required for inhibition are high relative to therapeutic concentrations, and hence, this action is probably of little or no clinical relevance. The lack of potentiation of the GABA receptor by MPA or its metabolites is surprising in consideration of the apparent anticonvulsant and anesthetic effects of MPA described above, and they remain unexplained.


title: Medroxyprogesterone acetate

text: Clinical studies using massive dosages of up to 5,000 mg/day oral MPA and 2,000 mg/day intramuscular MPA for 30 days in women with advanced breast cancer have reported "no relevant side effects", which suggests that MPA has no meaningful direct action on the GABA receptor in humans even at extremely high dosages.


title: Medroxyprogesterone acetate

text: Although MPA and the closely related medication megestrol acetate are effective appetite stimulants at very high dosages, the mechanism of action of their beneficial effects on appetite is not entirely clear. However, glucocorticoid, cytokine, and possibly anabolic-related mechanisms are all thought to possibly be involved, and a number of downstream changes have been implicated, including stimulation of the release of neuropeptide Y in the hypothalamus, modulation of calcium channels in the ventromedial hypothalamus, and inhibition of the secretion of proinflammatory cytokines including IL-1α, IL-1β, IL-6, and TNF-α, actions that have all been linked to an increase in appetite.


title: Medroxyprogesterone acetate

text: MPA weakly stimulates the proliferation of MCF-7 breast cancer cells "in vitro", an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1). Certain other progestins are also active in this assay, whereas progesterone acts neutrally. It is unclear if these findings may explain the different risks of breast cancer observed with progesterone, dydrogesterone, and other progestins such as medroxyprogesterone acetate and norethisterone in clinical studies.


title: Medroxyprogesterone acetate

text: Surprisingly few studies have been conducted on the pharmacokinetics of MPA at postmenopausal replacement dosages. The bioavailability of MPA with oral administration is approximately 100%. A single oral dose of 10 mg MPA has been found to result in peak MPA levels of 1.2 to 5.2 ng/mL within 2 hours of administration using radioimmunoassay. Following this, levels of MPA decreased to 0.09 to 0.35 ng/mL 12 hours post-administration. In another study, peak levels of MPA were 3.4 to 4.4 ng/mL within 1 to 4 hours of administration of 10 mg oral MPA using radioimmunoassay. Subsequently, MPA levels fell to 0.3 to 0.6 ng/mL 24 hours after administration. In a third study, MPA levels were 4.2 to 4.4 ng/mL after an oral dose of 5 mg MPA and 6.0 ng/mL after an oral dose of 10 mg MPA, both using radioimmunoassay as well.


title: Medroxyprogesterone acetate

text: Treatment of postmenopausal women with 2.5 or 5 mg/day MPA in combination with estradiol valerate for two weeks has been found to rapidly increase circulating MPA levels, with steady-state concentrations achieved after three days and peak concentrations occurring 1.5 to 2 hours after ingestion. With 2.5 mg/day MPA, levels of the medication were 0.3 ng/mL (0.8 nmol/L) in women under 60 years of age and 0.45 ng/mL (1.2 nmol/L) in women 65 years of age or over, and with 5 mg/day MPA, levels were 0.6 ng/mL (1.6 nmol/L) in women under 60 years of age and in women 65 years of age or over. Hence, area-under-curve levels of the medication were 1.6 to 1.8 times higher in those who were 65 years of age or older relative to those who were 60 years of age or younger. As such, levels of MPA have been found to vary with age, and MPA may have an increased risk of side effects in elderly postmenopausal women. This study assessed MPA levels using liquid-chromatography–tandem mass spectrometry (LC–MS/MS), a more accurate method of blood determinations.


title: Medroxyprogesterone acetate

text: Oral MPA tablets can be administered sublingually instead of orally. Rectal administration of MPA has also been studied.


title: Medroxyprogesterone acetate

text: With intramuscular administration of 150 mg microcrystalline MPA in aqueous suspension, the medication is detectable in the circulation within 30 minutes, serum concentrations vary but generally plateau at 1.0 ng/mL (2.6 nmol/L) for 3 months. Following this, there is a gradual decline in MPA levels, and the medication can be detected in the circulation for as long as 6 to 9 months post-injection. The particle size of MPA crystals significantly influences its rate of absorption into the body from the local tissue depot when used as a microcrystalline aqueous suspension via intramuscular injection. Smaller crystals dissolve faster and are absorbed more rapidly, resulting in a shorter duration of action. Particle sizes can differ between different formulations of MPA, potentially influencing clinical efficacy and tolerability.


title: Medroxyprogesterone acetate

text: The plasma protein binding of MPA is 88%. It is weakly bound to albumin and is not bound to sex hormone-binding globulin or corticosteroid-binding globulin.


title: Medroxyprogesterone acetate

text: The elimination half-life of MPA via oral administration has been reported as both 11.6 to 16.6 hours and 33 hours, whereas the elimination half-lives with intramuscular and subcutaneous injection of microcrystalline MPA in aqueous suspension are 50 and 40 days, respectively. The metabolism of MPA is mainly via hydroxylation, including at positions C6β, C21, C2β, and C1β, mediated primarily via CYP3A4, but 3- and 5-dihydro and 3,5-tetrahydro metabolites of MPA are also formed. Deacetylation of MPA and its metabolites (into, e.g., medroxyprogesterone) has been observed to occur in non-human primate research to a substantial extent as well (30 to 70%). MPA and/or its metabolites are also metabolized via conjugation. The C6α methyl and C17α acetoxy groups of MPA make it more resistant to metabolism and allow for greater bioavailability than oral progesterone.


title: Medroxyprogesterone acetate

text: MPA is eliminated 20 to 50% in urine and 5 to 10% in feces following intravenous administration. Less than 3% of a dose is excreted in unconjugated form.


title: Medroxyprogesterone acetate

text: With intramuscular administration, the high levels of MPA in the blood inhibit luteinizing hormone and ovulation for several months, with an accompanying decrease in serum progesterone to below 0.4 ng/mL. Ovulation resumes when once blood levels of MPA fall below 0.1 ng/mL. Serum estradiol remains at approximately 50 pg/mL for approximately four months post-injection (with a range of 10–92 pg/mL after several years of use), rising once MPA levels fall below 0.5 ng/mL.


title: Medroxyprogesterone acetate

text: Hot flashes are rare while MPA is found at significant blood levels in the body, and the vaginal lining remains moist and creased. The endometrium undergoes atrophy, with small, straight glands and a stroma that is decidualized. Cervical mucus remains viscous. Because of its steady blood levels over the long term and multiple effects that prevent fertilization, MPA is a very effective means of birth control.


title: Medroxyprogesterone acetate

text: MPA is a synthetic pregnane steroid and a derivative of progesterone and 17α-hydroxyprogesterone. Specifically, it is the 17α-acetate ester of medroxyprogesterone or the 6α-methylated analogue of hydroxyprogesterone acetate. MPA is known chemically as 6α-methyl-17α-acetoxyprogesterone or as 6α-methyl-17α-acetoxypregn-4-ene-3,20-dione, and its generic name is a contraction of 6α-methyl-17α-hydroxyprogesterone acetate. MPA is closely related to other 17α-hydroxyprogesterone derivatives such as chlormadinone acetate, cyproterone acetate, and megestrol acetate, as well as to medrogestone and nomegestrol acetate. 9α-fluoromedroxyprogesterone acetate (FMPA), the C9α fluoro analogue of MPA and an angiogenesis inhibitor with two orders of magnitude greater potency in comparison to MPA, was investigated for the potential treatment of cancers but was never marketed.


title: Medroxyprogesterone acetate

text: MPA was independently discovered in 1956 by Syntex and the Upjohn Company. It was first introduced on 18 June 1959 by Upjohn in the United States under the brand name Provera (2.5, 5, and 10 mg tablets) for the treatment of amenorrhea, metrorrhagia, and recurrent miscarriage. An intramuscular formulation of MPA, now known as DMPA (400 mg/mL MPA), was also introduced, under the brand name brand name Depo-Provera, in 1960 in the U.S. for the treatment of endometrial and renal cancer. MPA in combination with ethinylestradiol was introduced in 1964 by Upjohn in the U.S. under the brand name Provest (10 mg MPA and 50 μg ethinylestradiol tablets) as an oral contraceptive, but this formulation was discontinued in 1970. This formulation was marketed by Upjohn outside of the U.S. under the brand names Provestral and Provestrol, while Cyclo-Farlutal (or Ciclofarlutal) and Nogest-S were formulations available outside of the U.S. with a different dosage (5 mg MPA and 50 or 75 μg ethinylestradiol tablets).


title: Medroxyprogesterone acetate

text: Following its development in the late 1950s, DMPA was first assessed in clinical trials for use as an injectable contraceptive in 1963. Upjohn sought approval of intramuscular DMPA as a long-acting contraceptive under the brand name Depo-Provera (150 mg/mL MPA) in 1967, but the application was rejected. However, this formulation was successfully introduced in countries outside of the United States for the first time in 1969, and was available in over 90 countries worldwide by 1992. Upjohn attempted to gain FDA approval of DMPA as a contraceptive again in 1978, and yet again in 1983, but both applications failed similarly to the 1967 application. However, in 1992, the medication was finally approved by the FDA, under the brand name Depo-Provera, for use in contraception. A subcutaneous formulation of DMPA was introduced in the United States as a contraceptive under the brand name Depo-SubQ Provera 104 (104 mg/0.65 mL MPA) in December 2004, and subsequently was also approved for the treatment of endometriosis-related pelvic pain.


title: Medroxyprogesterone acetate

text: MPA has also been marketed widely throughout the world under numerous other brand names such as Farlutal, Perlutex, and Gestapuran, among others.


title: Medroxyprogesterone acetate

text: "Medroxyprogesterone acetate" is the generic name of the drug and its , , , and , while "medrossiprogesterone" is the and "médroxyprogestérone" the of its free alcohol form. It is also known as "6α-methyl-17α-acetoxyprogesterone" ("MAP") or "6α-methyl-17α-hydroxyprogesterone acetate".


title: Medroxyprogesterone acetate

text: MPA is marketed under a large number of brand names throughout the world. Its most major brand names are Provera as oral tablets and Depo-Provera as an aqueous suspension for intramuscular injection. A formulation of MPA as an aqueous suspension for subcutaneous injection is also available in the United States under the brand name Depo-SubQ Provera 104. Other brand names of MPA formulated alone include Farlutal and Sayana for clinical use and Depo-Promone, Perlutex, Promone-E, and Veramix for veterinary use. In addition to single-drug formulations, MPA is marketed in combination with the estrogens CEEs, estradiol, and estradiol valerate. Brand names of MPA in combination with CEEs as oral tablets in different countries include Prempro, Premphase, Premique, Premia, and Premelle. Brand names of MPA in combination with estradiol as oral tablets include Indivina and Tridestra.


title: Medroxyprogesterone acetate

text: Oral MPA and DMPA are widely available throughout the world. Oral MPA is available both alone and in combination with the estrogens CEEs, estradiol, and estradiol valerate. DMPA is registered for use as a form of birth control in more than 100 countries worldwide. The combination of injected MPA and estradiol cypionate is approved for use as a form of birth control in 18 countries.


title: Medroxyprogesterone acetate

text: Progestins in birth control pills are sometimes grouped by generation. While the 19-nortestosterone progestins are consistently grouped into generations, the pregnane progestins that are or have been used in birth control pills are typically omitted from such classifications or are grouped simply as "miscellaneous" or "pregnanes". In any case, based on its date of introduction in such formulations of 1964, MPA could be considered a "first-generation" progestin.


title: Medroxyprogesterone acetate

text: There was a long, controversial history regarding the approval of DMPA by the U.S. Food and Drug Administration. The original manufacturer, Upjohn, applied repeatedly for approval. FDA advisory committees unanimously recommended approval in 1973, 1975 and 1992, as did the FDA's professional medical staff, but the FDA repeatedly denied approval. Ultimately, on 29 October 1992, the FDA approved DMPA for birth control, which had by then been used by over 30 million women since 1969 and was approved and being used by nearly 9 million women in more than 90 countries, including the United Kingdom, France, Germany, Sweden, Thailand, New Zealand and Indonesia. Points in the controversy included:


title: Medroxyprogesterone acetate

text: DMPA was studied by Upjohn for use as a progestogen-only injectable contraceptive in women at a dose of 50 mg once a month but produced poor cycle control and was not marketed for this use at this dosage. A combination of DMPA and polyestradiol phosphate, an estrogen and long-lasting prodrug of estradiol, was studied in women as a combined injectable contraceptive for use by intramuscular injection once every three months.


title: Medroxyprogesterone acetate

text: High-dose oral and intramuscular MPA monotherapy has been studied in the treatment of prostate cancer but was found to be inferior to monotherapy with cyproterone acetate or diethylstilbestrol. High-dose oral MPA has been studied in combination with diethylstilbestrol and CEEs as an addition to high-dose estrogen therapy for the treatment of prostate cancer in men, but was not found to provide better effectiveness than diethylstilbestrol alone.


title: Medroxyprogesterone acetate

text: DMPA has been studied for use as a potential male hormonal contraceptive in combination with the androgens/anabolic steroids testosterone and nandrolone (19-nortestosterone) in men. However, it was never approved for this indication.


title: Medroxyprogesterone acetate

text: MPA was investigated by InKine Pharmaceutical, Salix Pharmaceuticals, and the University of Pennsylvania as a potential anti-inflammatory medication for the treatment of autoimmune hemolytic anemia, Crohn's disease, idiopathic thrombocytopenic purpura, and ulcerative colitis, but did not complete clinical development and was never approved for these indications. It was formulated as an oral medication at very high dosages, and was thought to inhibit the signaling of proinflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, with a mechanism of action that was said to be similar to that of corticosteroids. The formulation of MPA had the tentative brand names Colirest and Hematrol for these indications.


title: Medroxyprogesterone acetate

text: MPA has been found to be effective in the treatment of manic symptoms in women with bipolar disorder.


title: Medroxyprogesterone acetate

text: MPA has been used to reduce aggression and spraying in male cats. It may be particularly useful for controlling such behaviors in neutered male cats. The medication can be administered in cats as an injection once per month.


title: Scapegoating

text: Scapegoating is the practice of singling out a person or group for unmerited blame and consequent negative treatment. Scapegoating may be conducted by individuals against individuals (e.g. "he did it, not me!"), individuals against groups (e.g., "I couldn't see anything because of all the tall people"), groups against individuals (e.g., "He was the reason our team didn't win"), and groups against groups.


title: Scapegoating

text: A scapegoat may be an adult, child, sibling, employee, peer, ethnic, political or religious group, or country. A whipping boy, identified patient, or "fall guy" are forms of scapegoat.


title: Scapegoating

text: Scapegoated groups throughout history have included almost every imaginable group of people: genders, religions, people of different races, nations, or sexual orientations, people with different political beliefs, or people differing in behaviour from the majority. However, scapegoating may also be applied to organizations, such as governments, corporations, or various political groups.


title: Scapegoating

text: Jungian analyst Sylvia Brinton Perera situates its mythology of shadow and guilt. Individuals experience it at the archetypal level. As an ancient social process to rid a community of its past evil deeds and reconnect it to the sacred realm, the scapegoat appeared in a biblical rite, which involved two goats and the pre-Judaic, chthonic god Azazel. In the modern scapegoat complex, however, "the energy field has been radically broken apart" and the libido "split off from consciousness". Azazel's role is deformed into an accuser of the scapegoated victim.


title: Scapegoating

text: Blame for breaking a perfectionist moral code, for instance, might be measured out by aggressive scapegoaters. Themselves often wounded, the scapegoaters can be sadistic, superego accusers with brittle personas, who have driven their own shadows underground from where such are projected onto the victim. The scapegoated victim may then live in a hell of felt unworthiness, retreating from consciousness, burdened by shadow and transpersonal guilt, and hiding from the pain of self-understanding. Therapy includes modeling self-protective skills for the victim's battered ego, and guidance in the search for inner integrity, to find the victim's own voice.


title: Scapegoating

text: Unwanted thoughts and feelings can be unconsciously projected onto another who becomes a scapegoat for one's own problems. This concept can be extended to projection by groups. In this case the chosen individual, or group, becomes the scapegoat for the group's problems. "Political agitation in all countries is full of such projections, just as much as the backyard gossip of little groups and individuals." Swiss psychiatrist Carl Jung considered indeed that "there must be some people who behave in the wrong way; they act as scapegoats and objects of interest for the normal ones".


title: Scapegoating

text: The scapegoat theory of intergroup conflict provides an explanation for the correlation between times of relative economic despair and increases in prejudice and violence toward outgroups. Studies of anti-black violence (racist violence) in the southern United States between 1882 and 1930 show a correlation between poor economic conditions and outbreaks of violence (e.g., lynchings) against blacks. The correlation between the price of cotton (the principal product of the area at that time) and the number of lynchings of black men by whites ranged from −0.63 to −0.72, suggesting that a poor economy induced white people to take out their frustrations by attacking an outgroup.


title: Scapegoating

text: Scapegoating as a group necessitates that ingroup members settle on one specific target to blame for their problems. Scapegoating is also more likely to appear when a group has experienced difficult, prolonged negative experiences (as opposed to minor annoyances). When negative conditions frustrate a group's attempts at successful acquisition of its most essential needs (e.g., food, shelter), groups develop a compelling, shared ideology that – when combined with social and political pressures – may lead to the most extreme form of scapegoating: genocide.


title: Scapegoating

text: Scapegoating can also cause oppressed groups to lash out at other oppressed groups. Even when injustices are committed against a minority group by the majority group, minorities sometimes lash out against a different minority group in lieu of confronting the more powerful majority.


title: Scapegoating

text: Scapegoating has been noted after terrorist attacks and political assassinations; such as Anti-Arabism backlash against Arabs in America after September 11th, 2001, or the retaliations against the Sikhs in the wake of the assassination of Indira Gandhi in India.


title: Scapegoating

text: In management, scapegoating is a known practice in which a lower staff employee is blamed for the mistakes of senior executives. This is often due to lack of accountability in upper management.


title: Scapegoating

text: Literary critic and philosopher Kenneth Burke first coined and described the expression scapegoat mechanism in his books "Permanence and Change" (1935), and "A Grammar of Motives" (1945). These works influenced some philosophical anthropologists, such as Ernest Becker and René Girard.


title: Scapegoating

text: Girard developed the concept much more extensively as an interpretation of human culture. In Girard's view, it is humankind, not God, who has need for various forms of atoning violence. Humans are driven by desire for that which another has or wants (mimetic desire). This causes a triangulation of desire and results in conflict between the desiring parties. This mimetic "contagion" increases to a point where society is at risk; it is at this point that the "scapegoat mechanism" is triggered. This is the point where one person is singled out as the cause of the trouble and is expelled or killed by the group. This person is the scapegoat. Social order is restored as people are contented that they have solved the cause of their problems by removing the scapegoated individual, and the cycle begins again. The keyword here is "content".


title: Scapegoating

text: Scapegoating serves as a psychological relief for a group of people. Girard contends that this is what happened in the narrative of Jesus of Nazareth, the central figure in Christianity. The difference between the scapegoating of Jesus and others, Girard believes, is that in the resurrection of Jesus from the dead, he is shown to be an innocent victim; humanity is thus made aware of its violent tendencies and the cycle is broken. Thus Girard's work is significant as a reconstruction of the "Christus Victor" atonement theory.


title: Alexis Haines

text: Alexis Christine Haines (née Neiers; born June 20, 1991) is a member of the "Bling Ring" and a former television personality. At the age of 18, she was arrested for her involvement in a string of burglaries that targeted the homes of multiple celebrities. Haines served one month of a six-month sentence after her conviction for one count of first degree residential burglary.


title: Alexis Haines

text: Haines starred in the reality television show "Pretty Wild", but her struggles with addiction and the aftermath of being a part of the "Bling Ring" ended her Hollywood career goals. She got sober when she was 19, and started utilizing her platform to help others with drug problems, including becoming a columnist for "Vice". Haines began hosting the podcast "Recovering From Reality" in 2019"."


title: Alexis Haines

text: On November 16, 2009, Haines pleaded no contest to burglary charges stemming from her involvement with the Hollywood "Bling Ring" burglaries. The burglars had robbed the homes of celebrities including Orlando Bloom, Lindsay Lohan, Rachel Bilson, and Paris Hilton. Haines claimed to have been drunk during the burglary of Bloom's house, and "not sure what was going on". Co-defendant Nick Prugo recalled a different version of events, saying that Haines was fully aware a burglary was taking place, and is seen walking into the Bloom residence on security surveillance footage. A search of the Haines' household turned up a Marc Jacobs handbag belonging to Bilson and a Chanel necklace belonging to Lohan. Haines initially denied the items were stolen.


title: Alexis Haines

text: It appeared Haines was arrested on the set of reality show "Pretty Wild", during the taping of the pilot episode, but she and her mother revealed in the 2022 Netflix three-part docuseries "The Real Bling Ring: Hollywood Heist" that the arrest had occurred off-camera. Instead, the scene that aired on the show was a fabrication carried out by E!'s production crew. Haines also admitted that she was one of the tipsters who implicated Prugo in the security footage that aired on "TMZ".


title: Alexis Haines

text: On May 10, 2010, Haines pleaded no contest to a felony charge of first degree residential burglary of Orlando Bloom's home and was sentenced to 180 days in county jail, with three years' probation and a fine of $600,000. Haines began her sentence on June 24, 2010, and was released after serving one month of a six-month sentence. During the last five days of her sentence, she was in a cell next to Lindsay Lohan.


title: Alexis Haines

text: She reported that she did not have any contact with Lohan during her brief time in jail and that Lohan did not cause any trouble.


title: Alexis Haines

text: Haines has been featured in two films chronicling events surrounding the "Bling Ring", both titled "The Bling Ring".


title: Alexis Haines

text: In the first, a made for TV film that originally aired on Lifetime in 2011, the character based on her is named Maddie Bishop and is played by Spencer Locke.


title: Alexis Haines

text: British actress Emma Watson played Haines in the Sofia Coppola-directed 2013 film, wherein she is renamed as Nicolette "Nicki" Moore. The film premiered at the Cannes Film Festival, and was released nationwide on June 21, 2013. Haines has criticized her depiction in the film as inaccurate, alleging her role in the burglaries is exaggerated. Haines further called out Watson for negative comments Watson made about Haines' character in the film, saying she expected more empathy given the public knowledge that Haines had been sexually abused and was struggling with heroin addiction.


title: Alexis Haines

text: Haines was born to Mikel Neiers, a Hollywood cinematographer known for his roles as the director of photography on "Friends" and "Spin City", and Andrea Arlington, an actress and model who was in "Playboy" in the 1980s. They divorced, and Arlington remarried Jerry Dunn, a production designer for television, whom she later divorced.


title: Alexis Haines

text: Haines has said that she struggled with her father "falling off the face of this earth and not being a father."


title: Alexis Haines

text: Haines dropped out of Indian Hills High School to pursue a career in Hollywood, while studying for a GED under the supervision of her mother. She worked for some time as a hip-hop and pole dancing instructor. Haines obtained her GED at age 16. Haines alleges that when she was 16, Arlington took her and Taylor to get fake identification cards and pushed the teens into pin-up modeling, though Arlington denies this. Haines ultimately worked as a lingerie model, appeared in the straight-to-dvd film "Frat Party", and appeared nude behind a sheet in the Marilyn Manson music video for "Arma-goddamn-motherfuckin-geddon" when she was 17. At the time of the burglaries, Haines had been kicked out of her mother's and step-father's home, and was staying with "Bling Ring" co-defendant Nick Prugo and his family.


title: Alexis Haines

text: After the airing of "Pretty Wild", many unapproved images were released of Haines and her costar Tess Taylor on the website "TheDirty.com". Although lawyers requested that the images, which portrayed the girls smoking bongs and what appeared to be heroin, be taken down, blogger Nik Richie, the owner of the site, declined. In December 2010, Haines checked into the SOBA Recovery center in Malibu, California, after she was sentenced to one year of rehab following an arrest for possession of black tar heroin and a fake Florida identification card. Both were discovered when Haines failed to check in with her probation officer, while on probation for her involvement in the "Bling Ring", and officers paid her a visit and searched her residence. She was joined in rehab by Taylor, albeit briefly, under unrelated circumstances.


title: Alexis Haines

text: On December 8, 2011, Haines participated in an episode of Nik Richie radio on the website "TheDirty.com". She admitted to being addicted to heroin, Xanax, alcohol, and OxyContin during the filming of "Pretty Wild", stating that when not filming the show she was "living in a Best Western hotel", getting high and panhandling for money on the streets. She was sexually molested as a young child, which she says contributed to her drug problems, along with her troubles with her father, an incident of rape, and a boyfriend who also used. In 2011, she said she no longer speaks to Taylor, though in 2019, Taylor joined Haines on her podcast "Recovering from Reality" to discuss her recovery from her own heroin addiction. As of 2022, Haines said she had been sober for eleven years.


title: Alexis Haines

text: Haines got sober at nineteen years old, after facing up to six years in the California State prison system due to her addiction to heroin. Haines started school while in treatment in order to obtain her CASAC (Credentialed Alcohol and Substance Abuse Counselor) certification to become a licensed drug and alcohol counselor. Starting in 2013, Haines was a columnist for "Vice", covering youth, addiction, and recovery. She appeared in a documentary for "Vice", focusing on the heroin epidemic amongst youth in the Los Angeles area, and specifically, to show the human face of those in active addiction and hear their personal stories. Haines is now a counselor at Alo House Recovery Centers and hosts a podcast called "Recovering from Reality". Haines has also worked as a Doula.


title: Alexis Haines

text: In April 2012, she married Evan Haines, a Canadian businessman, in Mexico. There were 20 guests, including Haines' mother, Gabby, and Tess. On April 24, 2013, Haines gave birth to their first child, a girl. She later gave birth to their second child, another girl. In 2021, Haines and her husband separated, and as of September 2022, the relationship had ended, and Haines reported she had moved on with a "supportive" boyfriend.


title: Alexis Haines

text: On March 14, 2010, "Pretty Wild" premiered on E! network, a reality TV show based on the lives of Haines, her unofficially adopted "sister" Tess Taylor, her younger biological sister Gabby Neiers, and their mother, Andrea Arlington, a former "Playboy" model. The show focused on the modeling careers of Haines and Taylor, as well as their LA "party lifestyle". The show was criticized for the girls' sexual antics and the seemingly bizarre behavior of the sisters and their mother. Shortly after filming the pilot episode, Haines was arrested for her involvement in the "Bling Ring" robberies and the show ended up chronicling her arrest and eventual plea bargain and jail time. The show was not renewed for a second season.


title: Credit note

text: A credit note or credit memo is a commercial document issued by a seller to a buyer. Credit notes act as a source document for the sales return journal. In other words, the credit note is evidence of the reduction in sales. A credit memo, a contraction of the term "credit memorandum", is evidence of a reduction in the amount a buyer owes a seller under an earlier invoice.


title: Credit note

text: It can also be a document from a bank to a depositor to indicate the depositor's balance is being in the event other than a deposit, such as the collection by the bank of the depositor's note receivable.


title: Credit note

text: A credit note lists the products, quantities, and agreed prices for products or services the seller provided the buyer but the buyer returned or did not receive. It may be issued in the case of damaged goods, errors or allowances. In respect of the previously issued invoice, a Credit Memo will reduce or eliminate the amount the buyer has to pay. "Note:" A Credit Memo is not to be substituted as a formal document. The Credit Memo rarely contains PO #, Date, Billing Address, Shipping Address, Terms of Payment, List of products with quantities and prices. Usually, it references the original invoice and sometimes states the reason for the issue.


title: Rukhsar Rehman

text: Rukhsar Rehman (born 29 October 1975) is an Indian film & television actress and model in Bollywood. Rehman made her film debut in 1992 at the age of 17 with a lead role in Deepak Anand's "Yaad Rakhegi Duniya" opposite Aditya Pancholi and also appeared in J.K. Bihari's "Inteha Pyar Ki" opposite Rishi Kapoor. However, at the request of her father, she left her career and moved back to her hometown Rampur in Uttar Pradesh to start a garment business.


title: Rukhsar Rehman

text: In 2005, she returned to acting with Ram Gopal Verma's crime drama "D", in which she played Randeep Hooda's girlfriend. She also featured in Verma's "Sarkar" the same year. In 2008, she appeared in Rumi Jaffery's "God Tussi Great Ho" as Salman Khan's sister. In 2009, she starred in "The Stoneman Murders" alongside Kay Kay Menon. Film critic Taran Adarsh in his review for the film called her a "complete natural". She also had supporting roles in "Benny and Babloo" (2010), "Knock Out" (2010), "Allah Ke Banday" (2010), "Shaitan" (2011) and "PK" (2014).


title: Rukhsar Rehman

text: In television, she has featured in Sony Entertainment Television's medical drama "Kuch Toh Log Kahenge" (2011–13) as Dr. Mallika and in Life OK's "Tumhari Paakhi" (2013–14) as Lavanya. She did a cameo in Star Plus's "Diya Aur Baati" as Mehak. Rehman also did a critically acclaimed Malayalam film, "Take Off" (2017). She appeared in campaigns for brands like Kaya Skin Clinic, Asian Paints, Saffola salt and others.


title: Rukhsar Rehman

text: She has a daughter named Aisha Ahmed with her first husband Asad Ahmed. Aisha was recently seen in the movie "3 Storeys",a web series called "Adulting" on YouTube, and a "Shockers" season 1 skit, "Selfie", co-starring Amyra Dastur and Neha Mahajan.


title: Rukhsar Rehman

text: She was last seen in the Star Plus serial "Mariam Khan - Reporting Live" as the mother of the main protagonist.


title: Jaya Prada

text: Jaya Prada Nahata (born Lalitha Rani; 3 April 1962) is an Indian actress and politician. She is hailed as one of the most iconic and influential actresses in both Telugu and Hindi film industries in late '70s, '80s and early '90s. Jayaprada is the recipient of three Filmfare Awards South and has starred in many Telugu and Hindi films along with several Kannada, Tamil, Malayalam, Bengali and Marathi films. She left the film industry at the peak of her career, as she joined the Telugu Desam Party (TDP) in 1994 and entered politics. She was a Member of Parliament (MP) from Rampur, Uttar Pradesh from 2004 to 2014.


title: Jaya Prada

text: Some of her notable films include "Anthuleni Katha" (1976), "Siri Siri Muvva" (1976), "Sita Kalyanam" (1976), "Adavi Ramudu" (1977), "Yamagola" (1977), "Sanaadi Appanna" (1977), "Huliya Haalina Mevu" (1979), "Sargam" (1979), "Ooriki Monagadu" (1981), "Kaamchor" (1982), "Kaviratna Kalidasa" (1983), "Sagara Sangamam" (1983), "Tohfa" (1984), "Sharaabi" (1984), "Maqsad" (1984), "Sanjog" (1985), "Aakhree Raasta" (1986), "Simhasanam" (1986), "Sindoor" (1987), "Samsaram" (1988), "Elaan-E-Jung" (1989), "Aaj Ka Arjun" (1990), "Thanedaar" (1990), "Maa" (1991), "Habba" (1999), "Shabdavedhi" (2000), "Devadoothan" (2000), "Pranayam" (2011), "Ee Bandhana" (2007) and "Krantiveera Sangolli Rayanna" (2012). She won the Filmfare Award for Best Actress – Telugu for her performance in "Sagara Sangamam". She has also been awarded Filmfare Special Award for her performance in "Siri Siri Muvva" and "Anthuleni Katha".


title: Jaya Prada

text: She has been considered by many as one of the most beautiful face to have ever graced Indian cinema including Satyajit Ray who called her "the most beautiful face on the Indian screen".


title: Jaya Prada

text: Jayaprada was born as Lalitha Rani in Rajahmundry, Andhra Pradesh Rajaka family. Her father, Krishna Rao, was a Telugu film financier. Her mother, Neelavani, was a home-maker. Lalitha attended a Telugu medium school in Rajahmundry and was also enrolled in dance and music classes at an early age.


title: Jaya Prada

text: When Jayaprada was a teenager, she performed a dance at her school's annual function. A film director in the audience offered her a three-minute dance number in the Telugu film "Bhoomi Kosam" (1974). She was hesitant, but her family encouraged her to accept it. She was paid only 10 rupees for her work in the film, but the rushes of those three minutes of film were shown to the major figures of the Telugu film industry. Major filmmakers offered her starring roles in quality films, and she accepted them. She became a huge star in 1976 with major hit films. Director K. Balachander's black-and-white film "Anthuleni Katha" (1976) showcased her dramatic skills; K. Viswanath's colour film "Siri Siri Muvva" (1976) showed her playing a mute girl with excellent dancing skills; and her title role as Sita in the big-budget mythological film "Seetha Kalyanam" (1976) confirmed her versatility. In 1977, she starred in "Adavi Ramudu", which broke box office records and which permanently cemented her star status. The song "Aaresukoboyi Paresukunnanu" performed by Prada and co-star N.T. Rama Rao (NTR) became a mass hit. Important filmmakers were casting her and repeating her in their films. Filmmaker Vijay introduced her to Kannada cinema in his 1977 super-hit movie "Sanaadi Appanna" alongside Kannada matinee idol Dr. Rajkumar. The movie is also known to be the only movie to feature shehnai rendition by Ustad Bismillah Khan.


title: Jaya Prada

text: In 1979, K. Balachander repeated her in the Tamil film "Ninaithale Inikkum" opposite Kamal Haasan and Rajinikanth in which she played a terminally-ill patient. She continued to act in more films in Telugu opposite actors such as NTR, ANR, Krishna, Krishnam Raju and Sobhan Babu throughout the 70s and 80s. She acted in highest number of films with Krishna like "Sri Rajeshwari vilas coffee club" (1976), "Bhale Krishnudu" (1980), "Ooruki Monagadu" (1981), "Mundadugu" (1983), "Prajarajyam" (1983) and "Singhasan" (1986). K. Viswanath remade "Siri Siri Muvva" (1976) in Hindi as "Sargam", introducing Jayaprada to Bollywood in 1979. The film was successful and she became a star there as well. She earned her first Filmfare nomination as Best Actress but couldn't capitalize on her success since she couldn't speak Hindi.


title: Jaya Prada

text: In 1981, she starred in the critically acclaimed Tamil film "47 Natkal" and simultaneously made Telugu film "47 Rojulu" by filmmaker K. Balachander in which Chiranjeevi played her villainous, bigamist husband. After she took Hindi lessons, director K. Vishwanath relaunched her in Hindi films, with "Kaamchor" where she spoke Hindi fluently for the first time. "Saagara Sangamam" directed by K. Vishwanath, starring Kamal Haasan proved to be a milestone in her career, winning her many accolades including Filmfare Award for Best Actress - Telugu in 1983. She was now able to consistently work in Hindi films, and earned two more Filmfare nominations as Best Actress for playing Amitabh Bachchan's endearing girlfriend in Prakash Mehra's "Sharaabi" (1984) and for her challenging double role in K. Vishwanath's "Sanjog" (1985).


title: Jaya Prada

text: Jayaprada made a successful team not just with Amitabh Bachchan and Jeetendra, but also with her immediate screen rival Sridevi, with whom she has acted in about a dozen films. Their hit Telugu film "Devatha" (1982), where they played sisters who made huge sacrifices for each other, was remade into the hit Hindi film "Tohfa" (1984). These films endeared Jayaprada to the traditional conservative section of film goers and she amassed a huge female fan following as well. It was an image that would serve her well when she started a new career as a politician. In 1985, she acted in the Malayalam film "Iniyum Kadha Thudarum" directed by Joshiy starring Mammootty, Baby Shalini and Ambika.


title: Jaya Prada

text: Indian director Satyajit Ray described her as one of the prettiest women in the world. Although she has acted in Bengali films, she has never worked for Ray. (She claimed that Ray had her in mind for a film, but his illness and subsequent death prevented their collaboration).


title: Jaya Prada

text: Jayaprada continued to act as a heroine mainly opposite Amitabh and Jeetendra during the early 1990s. She also acted in some significant Kannada films as the heroine. From 1994 onwards, she cut back on film assignments and got more involved with a political career on call by her co-star NTR.


title: Jaya Prada

text: In 2000, she acted in the Malayalam film "Devadoothan", starring Mohanlal, directed by Sibi Malayil. The film garnered immensely popular reviews from the critics but failed at the box office. But it met with great appreciation from the audience when released in Home Media and when aired on television. his movie had evergreen hit songs. She also starred for the last time, opposite Kannada super star Dr. Rajkumar in Shabdavedi. In 2002, she stepped into the Marathi film industry by being a guest in the movie "Aadhaar". Thus far, she has acted in eight languages and has completed 300 films during a 30-year film career. In 2004, she acted in "Ee Snehatheerathu", a Malayalam film as Kunchacko Boban's mother. She started playing mature roles.


title: Jaya Prada

text: In 2011, she returned to Malayalam cinema with a strong role in "Pranayam", alongside Mohanlal and Anupam Kher. She played "Grace" in this film, which won her critical acclaim and several awards. Her 2012 Kannada film "Krantiveera Sangolli Rayanna" ("Sangolli Rayanna") that saw her donning the historical role of courageous Kittur Chennamma, completed 100 days at the box office.


title: Jaya Prada

text: On 22 February 1986, she married producer Srikanth Nahata, who was already married to Chandra and had 3 children. This marriage stirred a lot of controversy, especially since Nahata did not divorce his wife and had children with his first wife after marrying Jayaprada.


title: Jaya Prada

text: Jayaprada joined the Telugu Desam Party (TDP) in 1994 at the invitation of its founder N. T. Rama Rao, on the eve of the assembly elections, and rose quickly through the ranks. At that time there was speculation that she would run for election, but she preferred not to make her electoral debut, although she was offered a seat by Rao.


title: Jaya Prada

text: She campaigned in several constituencies in 1994. When Rao became the Chief minister in 1994, he appointed one of his sons-in-law Nara Chandrababu Naidu as the Revenue Minister. Soon after the formation of the government, Chandrababu Naidu convinced a majority of the TDP MLAs to elect him as the chief minister and revolted against his father in law. Since most of the legislators had gone over to his side, the Anti Defection Law did not apply and the Telugu Desam Party label passed on to the Chandrababu Naidu faction. During this period, Prada too joined the Chandrababu Naidu faction of the party. She was nominated to the Rajya Sabha representing Andhra Pradesh in 1996. She also held the post of Telugu Mahila President.


title: Jaya Prada

text: Following differences with party Supremo N. Chandrababu Naidu, she left the TDP to join Samajwadi Party. She contested from Rampur parliamentary Constituency in UP during the 2004 General election and got elected with a margin of more than 85000 votes. During her campaign for the Lok Sabha elections in 2009, she was issued a notice by the Election Commission for violating the code of conduct by distributing bindis to women in Rampur's Swar locality. On 11 May 2009, Jayaprada alleged that senior Samajwadi Party leader Azam Khan was distributing nude pictures of her. She was re-elected with a margin of more than 30,000 votes.


title: Jaya Prada

text: After she came out in open support of the former General Secretary of the Samajwadi Party, Amar Singh, Prada was expelled from the party on 2 February 2010 for allegedly indulging in anti-party activities and damaging the party's secular image. Amar Singh, along with Jayaprada floated his own political party, Rashtriya Lok Manch, in 2011, and fielded candidates in 360 of the 403 seats in Uttar Pradesh in the 2012 assembly polls. However, his party did not win a single seat in these elections. Later she, along with Amar Singh joined the RLD on 10 March 2014 and after that she got the ticket to contest from the Bijnor seat in the 2014 general elections. She, however, lost the election.


title: Jaya Prada

text: She joined the Bharatiya Janata Party in the presence of National General Secretary Bhupender Yadav on 26 March 2019.


title: The Mosquito

text: The Mosquito or Mosquito alarm is a machine used to deter loitering by emitting sound at high frequency. In some versions, it is intentionally tuned to be heard primarily by younger people. The devices have attracted controversy on the basis of human rights and discrimination concerns.


title: The Mosquito

text: Nicknamed "Mosquito" for the buzzing sound it plays, the device is marketed as a safety and security tool for preventing youths from congregating in specific areas. As such, it is promoted to reduce anti-social behaviour, such as loitering, vandalism, drug use, drug distribution, and violence. In the UK, over 3,000 have been sold, mainly for use outside shops and near transport hubs. The device is also sold in Australia, France, Denmark, Italy, Spain, Germany, Switzerland, Canada and the USA.


title: The Mosquito

text: Critics say that it discriminates against young people and infringes their human rights, while supporters argue that making the Mosquito illegal would infringe the rights of shopkeepers who suffer business losses when "unruly teenagers" drive away their customers. Mosquito distributors have said that they keep standards to ensure that the device is not abused, and Howard Stapleton who invented the device has asked European governments to legislate guidelines governing its use.


title: The Mosquito

text: The latest version of the device, launched late in 2008, has two frequency settings, one of approximately 17.4 kHz that can generally be heard only by young people, and another at 8 kHz that can be heard by most people. The maximum potential output sound pressure level is stated by the manufacturer to be 108 decibels (dB), and the manufacturer's product specification furthermore states that the sound can typically be heard by people below 25 years of age. The ability to hear high frequencies deteriorates in most humans with age (a condition known as presbycusis), typically observable by the age of 18.


title: The Mosquito

text: The Mosquito machine was invented and patented by Howard Stapleton in 2005, and was originally tested in Barry, South Wales, where it was successful in reducing teenagers loitering near a grocery store. The idea was born after he was irritated by a factory noise when he was a child. The push to create the product was when Stapleton's 17-year-old daughter went to the store to buy milk and was harassed by a group of 12 to 15-year-olds. Using his children as test subjects, he determined the frequency of "The Mosquito".


title: The Mosquito

text: The Mosquito was released to the mainstream market in 2005, through Stapleton's company Compound Security Solutions. The current device has two settings: the high frequency sound targeted at youth, and another that can be heard by everyone. The range of the sound is with the sound baffle, and without. It requires a 24-volt DC or 15-volt AC power supply.


title: The Mosquito

text: A device installed in a Spar shop in Caerleon Road in Newport, South Wales was banned after three months by the Newport Community Safety Partnership, a partnership set up to meet the requirements of the Crime and Disorder Act 1998, with members including Newport City Council, Gwent Police, Newport Local Health Board, South Wales Fire Service, representatives of Customs and Excise, and the Welsh Assembly Government. Despite the ban, another Spar shop in Newport installed the device. A Newport Community Safety Partnership spokesman said: "Any view expressed by the Partnership does not stop any business or private company from purchasing these devices. They must ensure these systems comply with the law."


title: The Mosquito

text: In February 2008, in response to a national campaign launched by the Children’s Commissioner for England, Liberty, and the National Youth Agency, the government issued a statement insisting that "'Mosquito alarms are not banned and the government has no plans to ban them".


title: The Mosquito

text: The sound was made into a mobile phone ringtone, which could not be heard by teachers if the phone rang during a class. Mobile phone speakers are capable of producing frequencies above 20 kHz. This ringtone became informally known as "Teen Buzz" or "the Mosquito ringtone" and has since been sold commercially.


title: The Mosquito

text: The Mosquito won the satirical Ig Nobel for "Peace" in 2006. The Ig Nobels celebrate the quirkier side of serious scientific endeavour, honouring "achievements that first make people laugh, and then make them think".


title: The Mosquito

text: The German Federal Institute for Occupational Safety and Health stated in a report on The Mosquito, entitled ""Use of ultrasonic noise channels not entirely safe"":


title: The Mosquito

text: In a United Kingdom survey of the relevant studies of adults exposed to high frequency sound in an occupational context for the Health and Safety Executive (HSE) in 2001, it was concluded that the studies were inadequate to establish guidelines for safe exposure. The Mosquito's manufacturer relies on these inconclusive adult studies to justify the safety of the device.


title: The Mosquito

text: The National Autistic Society said in 2008 that it was "extremely concerned" about possible harmful effects of the devices upon people with autism. Since autism causes auditory hypersensitivity, individuals with this disability can have more intense reactions to this sound, especially if they are also under 25. Since autism can also affect communication skills, some individuals may not be able to communicate their discomfort to caregivers. A supermarket in Longridge, England, removed a mosquito device in 2008 after a campaign by a 19-year-old Paul Brookfield, who has autism. Brookfield stated that the device was causing him pain due to his hypersensitivity.


title: The Mosquito

text: Other disabilities and conditions may be exacerbated by the device. In March 2009, a child who had recently undergone ear surgery reported that the device set off her tinnitus, causing significant pain.


title: The Mosquito

text: The Mosquito has received support and endorsements from municipalities, school districts, property management companies, convenience stores and other organisations. Rochdale Safer Communities Partnership said the borough was committed to the continued use of the Mosquito:


title: The Mosquito

text: "We feel totally justified in deploying Mosquito devices in the borough of Rochdale to give the community respite in cases of acute anti-social behaviour and youth nuisance," she said. "We use the devices when there are large groups of young people making life a problem for residents and businesses, as we are very keen not to let problems of anti-social behaviour escalate."


title: The Mosquito

text: The Association of Convenience Stores (ACS) also supports the usage of the device, and so does British Retail Consortium (BRC), stating that "Not all young people are involved in violence, but given that some retail staff are facing a level of insolence [from teenagers] they have to have the option of doing what they can to protect themselves. They are entitled to discourage threatening groups from hanging around or in their shops."


title: The Mosquito

text: At the Maple Ridge, Pitt Meadows and Vancouver west side school districts in British Columbia, Canada, the device has been credited with lowering exterior vandalism at one school by about 40%.


title: The Mosquito

text: Opposition categorises it as an indiscriminate sonic weapon which succeeds only in demonising children and young people and may breach their human rights. The National Youth Rights Association has met with some success fighting the devices in the United States.


title: The Mosquito

text: A UK campaign called "Buzz off" is calling for The Mosquito to be banned. Shami Chakrabarti, director of Liberty, has claimed that the sound is "untested [and] unregulated" and that it can be a "sonic weapon directed against children and young people." Albert Aynsley-Green, the former Children’s Commissioner for England, criticised the devices for indiscriminately targeting all children and babies regardless of their behaviour. He described such measures as "demonising children and young people", and creating a "dangerous and widening divide" between the young and the old.


title: The Mosquito

text: The device was singled out for criticism in a joint report by children's commissioners for all parts of the UK, which formed part of a United Nations review of standards in the UK. A report for the Council of Europe called for a ban in 2010, suggesting use of the Mosquito may breach human rights law.


title: The Mosquito

text: In January 2011, the device was banned on all Council and Partnership buildings in Sheffield following a successful campaign led by the then Member of UK Youth Parliament for Sheffield, Harrison Carter. Sheffield is the largest city in the country with such a ban in place. It was recognised by the UK Government in their Positive For Youth document, published by the Department for Education in January 2012. This strategy paper acts to set out a new-approach to cross government policy for young people aged 13–19. Although mentioned in the document, a national ban of the mosquito device was not in the Coalition Agreement, and is not part of current Government policy.


title: The Mosquito

text: In July 2014, a new campaign was started in order to get a mosquito device removed from the public library in Milford Haven, Pembrokeshire, and is ongoing.


title: The Mosquito

text: In 2016, a shopping centre in Queensland, Australia removed the device after two years of campaigning by a local lawyer, due to it discriminating against young people. It had been installed in the centre for 10 years.


title: The Mosquito

text: Campaigners and authorities in many countries have stated that they believe the device to breach human rights and may even constitute assault. Liberty has expressed concern that the device may violate sections 8 and 14 of the European Convention on Human Rights, and the United Kingdom's Human Rights Act 1998.


title: The Mosquito

text: The Committee on Culture, Science and Education of the Parliamentary Assembly of the Council of Europe prepared a report stating that this device violates many articles of both the European Convention on Human Rights and the United Nations Convention on the Rights of the Child, and should be banned in Europe, because it is often "painful" and causes "degrading and discriminatory consequences for young people". In September 2008, Baroness Sarah Ludford MEP moved a motion to the European Parliament to ban the use of the Mosquito. It failed to get enough signatures from MEPs to proceed to a full debate.


title: The Mosquito

text: In Belgium, a resolution was passed by the House in June 2008 asking the government to take all necessary measures to prohibit the use of devices like the Mosquito on Belgian territory. The legality of the device has also been tested in the French courts, where the Tribunal de Grande Instance de Saint-Brieuc prohibited the use of the Mosquito within its municipality, and ordered a private individual to pay €2,000 compensation after operating the device outside their house.


title: The Mosquito

text: Under Ireland's Non-Fatal Offences Against the Person Act, 1997, anyone who "directly or indirectly applies force to or causes an impact on the body of another... without the consent of the other" (force including "application of [any] form of energy"), is guilty of committing assault. This issue has been raised in relation to the Mosquito device by Ireland's Ombudsman for Children following legal advice provided by Youth Work Ireland, but has yet to be tested in the Irish courts.


title: The Mosquito

text: In the United Kingdom, the manufacturers claim that the tones are broadcast at 75 dB, meaning that the product falls within the government's auditory-safety limits, although the German news source Heise reported the device emits 85 dB, and websites selling the Mosquito claim it can go up to 95 dB with a special chip, which in reality allows the Mosquito to reach 104 dB. The government of the United Kingdom issued a statement in 2008 stating that "'Mosquito alarms are not banned and the government has no plans to ban them". The English county of Kent has chosen not to allow the usage of the Mosquito on council-owned buildings.


title: Jessi Slaughter cyberbullying case

text: The Jessi Slaughter cyberbullying case was an American criminal case that revolved around an 11-year-old named Jessica Leonhardt (known online as "Jessi Slaughter" and "Kerligirl13"), whose profanity-laden videos went viral on Stickam and YouTube in 2010. The videos were made in response to accusations that a friend had raped Leonhardt, and that Leonhardt had a sexual relationship with the lead singer of the electropop band Blood on the Dance Floor, a man named Dahvie Vanity (real name Jesus David Torres) while they were a minor. This resulted in a campaign of telephone and internet harassment against Leonhardt and their family, chiefly attributed to 4chan users and members of the internet-based group Anonymous. It began a debate about the dangers of anonymity on the Internet, and whether or not the Internet is a safe environment for minors, and all people in general.


title: Jessi Slaughter cyberbullying case

text: Leonhardt told "The Independent" in 2016: "I wouldn't even call what happened to me cyberbullying, it was straight up harassment and stalking. It started out as cyberbullying but it quickly evolved." Vanity has repeatedly denied all of the allegations against him. He has also denied knowing Leonhardt or any of the other victims that have accused him of sexual assault, rape, and child molestation and has stated that Leonhardt had a mental illness. The song "You Done Goofed" from the Blood on the Dance Floor album "Epic" is about Leonhardt and Vanity's alleged experiences with them.


title: Jessi Slaughter cyberbullying case

text: Assigned female at birth, Leonhardt later came out as transgender and non-binary, now going by the name Damien Leonhardt. In 2018, they accused Vanity of child sexual abuse and rape in a post on social media site Tumblr during their alleged relationship, when Leonhardt was 10 years old. One year later, an additional 21 women accused Vanity of sexual assault, child molestation, and rape, with many of them saying the attacks took place while they were under the age of consent.


title: Jessi Slaughter cyberbullying case

text: Leonhardt began making YouTube videos when they were 10 years old, discussing "fashion, clothes and local drama that was happening within the party scene" which were uploaded on their friend's webcam. Leonhardt posted their first popular video just before their twelfth birthday in response to two claims made on StickyDrama and MySpace: the first being that they were a victim of rape, and the second being that they were having an underaged sexual relationship with the lead singer of the electronic band Blood on the Dance Floor, a man by the name of Dahvie Vanity (real name Jesus David Torres). The video was eventually linked to by users of 4chan, who then found and distributed Leonhardt's real name, phone number and address. Leonhardt also responded to comments that their relationship with Vanity constituted statutory rape with anger.


title: Jessi Slaughter cyberbullying case

text: The harassment intensified after Leonhardt uploaded a video that included their father, Gene Leonhardt, insulting and threatening the 4chan users that had posted information about Leonhardt, telling them that they had "done goofed", and that:


title: Jessi Slaughter cyberbullying case

text: The video, which was titled "You Dun Goofed Up", received over 1 million views on YouTube in one week. Leonhardt's father's reaction made the taunting worse, and the video of his reactions received more views than any of Leonhardt's previous recordings, with several quotes from his speech, "Consequences will never, be, the same!" and "You've been reported to the cyber police!" in particular, becoming memes themselves. Gene was later arrested in March 2011 for abusing Leonhardt in an argument when he punched them, causing them to have bloody and swollen lips, according to a police report. Gene later died from a heart attack while in custody at a police station in early 2011.


title: Jessi Slaughter cyberbullying case

text: Leonhardt stated that they had lost all of their friends as a result of the harassment. Because of the harassment, Leonhardt was placed under police protection, and the family's home under police surveillance. Leonhardt underwent counseling for harassment. In a subsequent "Good Morning America" interview, the family revealed that they have received harassment, including death threats. The Marion County, Florida sheriff's department said it was investigating allegations that there were pornographic photos of Leonhardt online. In retaliation for Gawker's coverage of the case, Gawker experienced a series of DoS attacks attributed to 4chan users.


title: Jessi Slaughter cyberbullying case

text: After the "Good Morning America" interview, the television audience was given advice on how to handle cyberbullying (online bullying and harassment) from internet privacy expert Parry Aftab. Aftab was subsequently subjected to harassment attributed to 4chan users in the forms of Google bombing false accusations of child sexual assault, the distribution of personal information, threatening telephone calls, and DoS attacks against her websites "wiredsafety.org" and "aftab.com". Aftab canceled a follow-up "GMA" report due to air the next day because of the harassment.


title: Jessi Slaughter cyberbullying case

text: In Australia, advocates of internet censorship invoked the harassment to support mandatory content filtering. In France, "L'Express" described the harassment as "ruining the life" of "an American in the midst of an adolescent crisis", and France24 noted that some were using the controversy to claim that 4chan should be censored.


title: Jessi Slaughter cyberbullying case

text: The case was seen by "BuzzFeed News" in 2018 as an example of how attitudes to cyberbullying have changed since 2010, with more emphasis on the victim of abuse.


title: Jessi Slaughter cyberbullying case

text: Rumors of rape and sexual abuse by Vanity had been circulating since 2009. Blood on the Dance Floor members Garrett Ecstasy, who left the band in 2009, and Jayy Von Monroe, who left the band in 2016, have described Vanity as a sexual predator. Jeffree Star and New Years Day members Ash Costello and Nikki Misery have stated that they observed Vanity engage in questionable or illegal sexual behavior during one of the Vans Warped Tours and also during an "All the Rage Tour 2012" around the early 2010s.


title: Jessi Slaughter cyberbullying case

text: On March 2, 2018, Leonhardt made a Tumblr post in which they publicly accused Vanity of rape for the first time.


title: Jessi Slaughter cyberbullying case

text: In March 2020, Leonhardt told journalist Chris Hansen of "To Catch A Predator" that Vanity sexually assaulted them in April 2009, when Leonhardt was 10 and Vanity was 24. They were interviewed as part of Hansen's YouTube channel "Have A Seat With Chris Hansen"; Hansen described Leonhardt as Vanity's "victim zero". Leonhardt said they were at a party at which Vanity was present and while they were in the bathroom of the house, Vanity coerced them to perform oral sex on him. During the next 16 months, Leonhardt stated that Vanity had violently raped them under the guise of BDSM style sexual activity. In 2010, Leonhardt told a classmate that Vanity had molested them, but later told "Insider" that they used the term as a joke, and viewed the relationship as consensual. Leonhardt also stated that had they not mentioned Vanity to classmates – which led to the case being discussed online – the abuse would have continued. One year later, 21 women accused Vanity of sexual assault, child molestation, and rape with many of the women saying that the attacks had taken place while they were under the age of consent. This led to the FBI beginning an investigation into the allegations against Vanity.


title: Spike Dudley

text: Matthew Jonathan Hyson (born August 13, 1970) is an American retired professional wrestler best known for his tenure in World Wrestling Entertainment (WWE) as Spike Dudley. Prior to WWE, Hyson began performing as Spike Dudley in the 1990s with Extreme Championship Wrestling (ECW); the Spike Dudley character being a member of The Dudley Brothers. As part of a storyline, fellow members Bubba Ray Dudley and D-Von Dudley betrayed the faction to form a separate Dudley Boyz tag team; resulting in Hyson and members being involved in a subsequent feud with the duo.


title: Spike Dudley

text: The Dudley Boyz would eventually leave ECW for the World Wrestling Federation (WWF) in 1999. Meanwhile, Hyson remained in ECW, and during his time held two reigns as ECW World Tag Team Champion alongside Balls Mahoney. The promotion fell into bankruptcy in 2001, which led Hyson to join the WWF, where he reconciled with Ray and D-Von. Hyson would appear with his kayfabe brothers on-and-off, as well as capturing the WWF Tag Team Championship with Tazz. Hyson also held the European Championship once and Hardcore Championship eight times in 2002. He would go on to team with Ray and D-Von following this, and would then have a singles career in the promotion from 2004 to 2005, notably holding the Cruiserweight Championship.


title: Spike Dudley

text: In 2005, Hyson was released from his WWE contract. After a brief stint on the independent circuit and becoming a trainer at The Lock-Up Wrestling School, Hyson would join Total Nonstop Action Wrestling (TNA) changing his ring name to Brother Runt due to WWE retaining the Dudley trademark. He once again teamed with Ray and Devon who had joined the promotion a few months prior to him; as well as feuding with Abyss. Following his release from TNA in the summer of 2007, Hyson continued to work as a trainer, and would continue to compete on the independent circuit simply as Matt Hyson until 2010 where he stopped training and performing on a full-time basis, with his final match occurring in 2015.


title: Spike Dudley

text: In May 1993, Hyson entered All Pro Wrestling's "Boot Camp" in Hayward, California to train as a referee and manager. He quickly began training to be a wrestler as well and spent the next three years wrestling for independent California promotions.


title: Spike Dudley

text: Hyson debuted in Extreme Championship Wrestling on September 14, 1996, at When Worlds Collide II. He was introduced as a fan favorite under the ring name "Little" Spike Dudley, as a part of the Dudley family. In his debut match, Spike teamed with his storyline brother Bubba Ray Dudley to defeat The Erotic Experience (GQ Gorgeous and Pat Day). He made his televised debut in ECW on the October 1 episode of "Hardcore TV". His in-ring persona was that of the "runt" of the family. His initials LSD and finishing move, the "Acid Drop" were both drug references and, at times, he would stare at his hands waving in front of him as if he were on a trip.


title: Spike Dudley

text: At Crossing the Line Again on February 1, 1997, Bubba turned on the Dudley family by aligning with D-Von Dudley and hitting a "Dudley Death Drop" on Spike and forming the tag team The Dudley Boyz. This also resulted in Spike becoming the first recipient of the "Dudley Death Drop" or "3D". As a result, Spike began a lengthy on-and-off scripted rivalry with them which continued for two years.


title: Spike Dudley

text: Spike would lose to Dudley Boyz' ally Axl Rotten on a few occasions at "Winter Blowout" and CyberSlam. During the summer of 1997, Spike teamed with Mikey Whipwreck and got involved in a mini feud with PG-13, which resulted in Dudley and Whipwreck defeating PG-13 at Heat Wave. Dudley's first high-profile feud began with Bam Bam Bigelow when Dudley defeated Bigelow to score an upset win at Born to be Wired. He quickly gained the nickname "The Giant Killer", as he would be booked to score quick wins against larger and heavier opponents. Dudley lost to Bigelow in a rematch in his pay-per-view debut at Hardcore Heaven. At As Good as It Gets, Dudley lost to Bigelow in a match. The match was notable for a very interesting moment in not only Hyson's career but in ECW history in general, in which Bigelow threw him from the ring over the top rope and into the crowd. The fans caught him and proceeded to body surf him around the ECW Arena. This incident was incorporated into the "Hardcore TV" introduction for years.


title: Spike Dudley

text: Teaming with multiple people, including Tommy Dreamer, The Sandman, New Jack, and Nova, he defeated them to win the ECW World Tag Team Championship with his partner Balls Mahoney on two occasions in 1999.


title: Spike Dudley

text: He was also in the main event on some occasions, such as the 2000 Guilty as Charged pay-per-view, where he faced Mike Awesome for the ECW World Heavyweight Championship, in a losing effort. During the match, however, he injured his knee, and after aggravating the injury in subsequent matches with Awesome and Lance Storm was forced to take several months off to recuperate. He returned in June 2000 as the ECW Commissioner and returned to in-ring action at the November to Remember event of that year, relinquishing his role as commissioner. Hyson stayed with ECW until it folded in 2001.


title: Spike Dudley

text: Dudley joined the WWF in 2001, aligning with his half-brothers, Bubba Ray and D-Von. With his brothers in the middle of a three-way feud for the WWF Tag Team Championship with the Hardy Boyz and Edge & Christian, Dudley frequently battled with Lita and Rhyno to try and help their respective team win (Lita managed The Hardy Boyz while Rhyno managed Edge & Christian). Notably all three were heavily involved in the Tables, Ladders and Chairs (TLC) match at WrestleMania X-Seven. Although Dudley inadvertently saved Lita from being taken out by Rhyno, Dudley later took a hard chair shot to the head from Lita (who was later taken out by Bubba Ray and D-Von) and was then taken out by Jeff Hardy when he performed a Swanton Bomb off a 20-foot ladder and landed on 2 parallel tables with Rhyno on one and Dudley on the other with Jeff mostly landing on Dudley's table.


title: Spike Dudley

text: After WrestleMania, The Dudley Boyz began a feud with The Holly Cousins. During this time, Dudley began a relationship with Molly Holly, which led to the Dudleys turning on him and putting Holly through a table. On the June 14 episode of "SmackDown!", Dudley was given his first opportunity at the WWF Championship, in a losing effort against Stone Cold Steve Austin. During The Invasion, Dudley remained loyal to WWF, despite being an ECW alumnus. It was during The Invasion that his relationship with Molly came to an end when she turned on him, aligning herself with Hurricane Helms and joining The Alliance.


title: Spike Dudley

text: Between May 2001 and January 2002, Dudley formed short-lived tag teams in an attempt to defeat his brothers. On the January 7, 2002 edition of "Raw", Dudley and Tazz defeated The Dudley Boyz for the WWF Tag Team Championship, and successfully retained them at the Royal Rumble. Dudley next entered the Hardcore Championship picture, winning the championship eight times, including at WrestleMania X8 (though he never held the championship for more than a day, due to the "24/7 rule.") He also defeated William Regal for the European Championship on the April 8 episode of "Raw", and held the championship for a month before losing it back to Regal.


title: Spike Dudley

text: As 2002 went along, Spike and Bubba began to team together again and feuded with The Un-Americans while also pursuing the WWE Tag Team Championship. By the end of the year, D-Von had rejoined his brothers, and they feuded with 3-Minute Warning. Dudley was injured after a missed spot during a 10-man tag match on "Raw" in September 2003. La Résistance threw Dudley to the outside but Dudley missed the table that he was supposed to crash through. After some time away from the ring, Spike returned and defeated René Duprée to get revenge for the injury.


title: Spike Dudley

text: In 2004, Dudley was drafted to the SmackDown! brand, where he immediately began challenging for the WWE Cruiserweight Championship. On the July 29 episode of "SmackDown!", he defeated Rey Mysterio for the championship with interference from his brothers, thus turning into a heel. He then began to wrestle as the "boss" of the Dudley Boyz. The Dudleys defeated Mysterio, Billy Kidman and Paul London in a six-man tag team match at SummerSlam. He continued to defend his championship throughout the year, before eventually losing the Cruiserweight Championship to Funaki at Armageddon.


title: Spike Dudley

text: He made his last appearance with WWE at ECW One Night Stand on June 12, 2005, helping the Dudleys win their tag team match. At the event, Spike was dressed like his old ECW character (tie-dyed shirt and overalls) but still portrayed his WWE "Boss" character. Dudley was released from his WWE contract on July 5, 2005, along with seven other wrestlers in what was thought to have been a cost-cutting measure by the company. Bubba and D-Von also departed the company after ECW One Night Stand.


title: Spike Dudley

text: Hyson debuted in Total Nonstop Action Wrestling on the April 14, 2006 episode of "TNA Impact!", preventing Eric Young from driving Brother Devon through a table and attacking each member of Team Canada. Hyson then celebrated with Brother Devon and Brother Ray, with him identifying him as "Brother Spike" and then "Brother Runt". At Lockdown, Runt and Team 3D defeated Team Canada in a Six Sides of Steel Anthem match. Brother Runt continued to be a part of Team 3D during feud with Abyss and the James Gang and at Victory Road, Runt and Team 3D lost a six-man tag to The James Gang and Abyss. At Hard Justice, Runt lost to Abyss. On the August 31 episode of "Impact!", Runt lost to Abyss in a 10,000 Thumbtacks match.


title: Spike Dudley

text: In June 2006, Hyson represented TNA in Japan with the Hustle federation, where he, alongside Ray and Devon, defeated Kouhiro Kanemura, Masato Tanaka and Tomoaki Honma twice in 3-on-3 tag-team matches.


title: Spike Dudley

text: At UFW's "Hardcore War" show, Spike stated that he had been sent a contract to compete at WWE's ECW One Night Stand. Spike took out the contract and tore it into pieces in front of the live crowd stating that he was remaining loyal to TNA.


title: Spike Dudley

text: Through the rest of the year, Brother Runt continued to feud with Abyss and several other heavyweight wrestlers while having a short-lived alliance with Raven (Raven saved Brother Runt from being smashed through two stacked tables covered in thumbtack-covered boards from Abyss, before throwing Abyss in himself), before he turned on Raven on September 15, 2006. In September and October 2006 Hyson had formed a new look, very similar to Travis Bickle in the hit 1976 movie Taxi Driver complete with Bickle's trademark green army jacket and mohawk. At No Surrender, Brother Runt competed in a No Disqualification 3-Way Dance which was won by Abyss, At Bound for Glory, Brother Runt competed in a fatal four way Monster's Ball match which was won by Samoa Joe. On the December 21 episode of "Impact!" Brother Runt made his first TNA appearance in a while dressed up as Santa Claus, and was subsequently beaten down by The Latin American Xchange (LAX) until being saved by Eric Young, Sonjay Dutt, Jay Lethal, and Petey Williams. On the January 4 episode of "Impact!", Runt lost to Homicide in a Mexican Street Fight.


title: Spike Dudley

text: At Final Resolution on January 21, 2007, a drunk Brother Runt cost his Team 3D teammates their NWA World Tag Team Championship match against LAX (Latin American Exchange) by jumping onto Homicide. Runt soon returned to the April 12 episode of "Impact!" after being attacked by LAX backstage. He was mocked by Konnan who fired a taser gun at him causing Brother Runt to roll around in pain. On August 15, 2007, Runt was released from TNA after several months of inactivity.


title: Spike Dudley

text: On April 16, 2009, Brother Runt and Balls Mahoney appeared on "TNA Impact!" to wish Team 3D luck in their match at Lockdown. They later were attacked by Beer Money, Inc. On March 15, 2010's episode of "Impact!" in a six-man tag team match, he and Team 3D were defeated by The Nasty Boys and Jimmy Hart. On August 4, 2010, it was confirmed that Hyson would be taking part in TNA's ECW reunion show, Hardcore Justice. At Hardcore Justice Hyson, was defeated by Rhino in a three-way match, which also included Al Snow.


title: Spike Dudley

text: On January 17, 2013, Hyson made an appearance on TNA "Impact Wrestling" as one of Bully Ray's groomsmen during his wedding to Brooke Hogan. He was assaulted by Aces & Eights after they crashed the ceremony. On March 19, 2013, Runt appeared at TNA Hardcore Justice 2, teaming with Jeff Hardy to defeat Team 3D (Bully Ray and Devon) in a tag team tables match, which aired on July 5, 2013.


title: Spike Dudley

text: Upon leaving WWE, he billed himself as Matt Hyson and performed at independent shows, mainly Top Rope Promotions in Massachusetts. He also joined the roster for Squared Circle Wrestling (2CW) in Syracuse, New York and the New York Wrestling Connection in Deer Park, New York. Hyson also went on to wrestle at Shane Douglas' Hardcore Homecoming, as well as guest featuring at shows with large amounts of talent from Total Nonstop Action Wrestling (TNA), mainly the UWF (UWF Live); this building speculation that Hyson would be signing with the TNA promotion. Whilst under contract with TNA, Hyson was permitted to continue his work for independent wrestling companies, and would use his TNA ringname Brother Runt instead of Matt Hyson.


title: Spike Dudley

text: In mid-2006, Hyson trained professional wrestlers at Top Rope Promotions in Fall River, Massachusetts until 2010.