<unk>  have relatively few side effects at typical dosages. Side effects of<unk>  may include tiredness, dysphoria, depression, mood changes, menstrual irregularities, hypomenorrhea, edema, vaginal dryness, vaginal atrophy, headaches, nausea, breast tenderness, decreased libido. Progestins with androgenic activity, namely 19-nortestosterone derivatives, can also cause acne, hirsutism, seborrhea, voice deepening, changes in liver protein production (e.g., decreased HDL cholesterol, sex hormone-binding globulin), increased appetite, and weight gain, among others. Other side effects of<unk>  may include an increased risk of breast cancer, cardiovascular disease, and blood clots, among others. Some of the side effects of<unk>  are due not to their<unk> c activity but rather due to off-target activities (e.g., androgenic activity, glucocorticoid activity, antimineralocorticoid activity). At high doses, due to their antigonadotropic effects,<unk>  can cause low sex hormone levels and associated side effects like diminished secondary sexual characteristics, sexual dysfunction (e.g., reduced sex drive and erectile dysfunction), reversible infertility, reduced bone mineral density, and an increased risk of bone fractures, both in men and in premenopausal women. Mood changes Birth control The available evidence on the risk of mood changes and depression with<unk>  in hormonal birth control is limited. As of 2019, there is no consistent evidence for adverse effects on mood of hormonal birth control, including<unk> only birth control and combined birth control, in the general population. Most women taking combined birth control experience no influence or a beneficial effect on mood. Adverse effects on mood appear to be infrequent, occurring only in a small percentage of women. About 5 to 10% of women experience negative mood changes with combined birth control pills, and about 5% of women discontinue birth control pills due to such changes. A study of about 4,000 women found that<unk> only birth control with depot medroxyprogesterone acetate had an incidence of depression of 1.5% and discontinuation due to depression of 0.5%. Beneficial effects of hormonal birth control such as decreased menstrual pain and bleeding may positively influence mood. A 2018 systematic review of 26 studies, including 5 randomized controlled trials and 21 observational studies, found that the overall evidence showed no association between<unk> only birth control and depression. The progestins assessed included depot medroxyprogesterone acetate, levonorgestrel-containing contraceptive implants and intrauterine devices, and<unk> only birth control pills. Findings of large observational studies are mixed due to prominent confounding factors, but overall show no association of hormonal birth control with depression. Randomized controlled trials typically do not find clinically significant influences of hormonal birth control on mood. Reviews from before 1980 reported a high incidence of adverse mood effects with combined birth control pills. However, doses of estrogens and<unk>  in birth control pills before 1980 were considerably higher than those used today, and these doses frequently caused unpleasant side effects that may have unfavorably influenced mood. Mood with birth control pills may be better with monophasic and continuous formulations than with triphasic and cyclic formulations. Limited and inconsistent evidence supports differences in mood with hormonal birth control using different doses of ethinylestradiol or different routes of administration, such as birth control pills versus contraceptive vaginal rings and contraceptive patches. Combined birth control with less androgenic or antiandrogenic progestins like desogestrel, gestodene, and drospirenone may have a more favorable influence on mood than birth control with more androgenic progestins like levonorgestrel. However, androgen supplementation with hormonal birth control has also been reported to improve mood. Hormonal birth control that suppresses ovulation is effective in the treatment of premenstrual dysphoric disorder (PMDD). Combined birth control pills containing drospirenone are approved for the treatment of PMDD and may be particularly beneficial due to the antimineralocorticoid activity of drospirenone. Studies on the influence of hormonal birth control on mood in women with existing mood disorders or polycystic ovary syndrome are limited and mixed. Women with underlying mood disorders may be more likely to experience mood changes with hormonal birth control. A 2016 systematic review found based on limited evidence from 6 studies that hormonal birth control, including combined birth control pills, depot medroxyprogesterone acetate, and levonorgestrel-containing intrauterine devices, was not associated with worse outcomes compared to non-use in women with depressive or bipolar disorders. A 2008 Cochrane review found a greater likelihood of postpartum depression in women given norethisterone enanthate as a form of<unk> only injectable birth control, and recommended caution on the use of<unk> only birth control in the postpartum period. Studies suggest a negativity bias in emotion recognition and reactivity with hormonal birth control. Some data suggests blunted reward responses and potential dysregulation of the stress response with hormonal birth control in some women. Hormone therapy Estrogen therapy appears to have a beneficial influence on mood in depressed and euthymic perimenopausal women. Conversely, research on combined estrogen and<unk> therapy for depressive symptoms in menopausal women is scarce and inconclusive. Some researchers contend that<unk>  have an adverse influence on mood and reduce the benefits of estrogens on mood, whereas other researchers maintain that<unk>  have no adverse influence on mood. Progesterone differs from progestins in terms of effects in the brain and might have different effects on mood in comparison. The available evidence, although limited, suggests no adverse influence of progesterone on mood when used in menopausal hormone therapy. Sexual function In most women, sexual desire is unchanged or increased with combined birth control pills. This is despite an increase in sex hormone-binding globulin (SHBG) levels and a decrease in total and free testosterone levels. However, findings are conflicting, and more research is needed. Blood clots Venous thromboembolism (VTE) consists of deep vein thrombosis (DVT) and pulmonary embolism (PE). DVT is a blood clot in a deep vein, most commonly in the legs, while PE occurs when a clot breaks free and blocks an artery in the lungs. VTE is a rare but potentially fatal cardiovascular event. Estrogens and<unk>  can increase coagulation by modulating synthesis of coagulation factors. As a result, they increase the risk of VTE, especially during pregnancy when estrogen and progesterone levels are very high as well as during the postpartum period. Physiological levels of estrogen and/or progesterone may also influence risk of VTE—with late menopause (≥55 years) being associated with greater risk than early menopause (≤45 years).<unk> monotherapy<unk>  when used by themselves at typical clinical dosages, for instance in<unk> only birth control, do not affect coagulation and are not generally associated with a higher risk of venous thromboembolism (VTE). An exception is medroxyprogesterone acetate as a<unk> only injectable contraceptive, which has been associated with a 2- to 4-fold increase in risk of VTE relative to other<unk>  and non-use. The reasons for this are unknown, but the observations might be a statistical artifact of preferential prescription of depot medroxyprogesterone acetate to women at risk for VTE. Alternatively, medroxyprogesterone acetate may be an exception among<unk>  in terms of influence on VTE risk, possibly due to its partial glucocorticoid activity. In contrast to depot medroxyprogesterone acetate, no increase in VTE risk has been observed with moderately high doses of the related progestin chlormadinone acetate (10 mg/day for 18–20 days/cycle), though based on limited data. Very-high-dose<unk> therapy, including with medroxyprogesterone acetate, megestrol acetate, and cyproterone acetate, has been associated with activation of coagulation and a dose-dependent increased risk of VTE. In studies with high-dose cyproterone acetate specifically, the increase in VTE risk has ranged from 3- to 5-fold. The incidence of VTE in studies with very-high-dose<unk> therapy has been found to range from 2 to 8%. However, the relevant patient populations, namely aged individuals with cancer, are already predisposed to VTE, and this greatly amplifies the risk. Estrogen plus<unk> therapy In contrast to<unk> only birth control, the addition of progestins to oral estrogen therapy, including in combined birth control pills and menopausal hormone therapy, is associated with a higher risk of VTE than with oral estrogen therapy alone. The risk of VTE is increased by about 2-fold or less with such regimens in menopausal hormone therapy and by 2- to 4-fold with combined birth control pills containing ethinylestradiol, both relative to non-use. In contrast to oral estrogen therapy, parenteral estradiol, such as with transdermal estradiol, is not associated with a higher risk of VTE. This is likely due to its lack of first-pass effect in the liver. Research is mixed on whether addition of progestins to transdermal estradiol is associated with a greater risk of VTE, with some studies finding no increase in risk and others finding higher risk. Unlike the case of transdermal estradiol, VTE risk is not lower with ethinylestradiol-containing contraceptive vaginal rings and contraceptive patches compared to combined birth control pills with ethinylestradiol. This is thought to be due to the resistance of ethinylestradiol to hepatic metabolism. The type of progestin in combined birth control may modulate the risk of VTE. Studies have found that combined birth control pills containing newer-generation progestins such as desogestrel, gestodene, norgestimate, drospirenone, and cyproterone acetate are associated with a 1.5- to 3-fold higher risk of VTE than birth control pills containing first-generation progestins such as levonorgestrel and norethisterone.
Progestogen 
Norgesterone
Antigonadotropin
Catechol estrogen
Androgen
Haloprogesterone
Vinyltestosterone
Androstenediol