Approved uses of<unk>  in the United States include short-term treatment of menopausal symptoms such as hot flashes and vaginal atrophy, and prevention of osteoporosis. The American College of Obstetrics and Gynecology (ACOG) approves of<unk>  for symptomatic relief of menopausal symptoms, and advocates its use beyond the age of 65 in appropriate scenarios. The North American Menopause Society (NAMS) 2016 annual meeting mentioned that<unk>  may have more benefits than risks in women before the age of 60. A consensus expert opinion published by The Endocrine Society stated that when taken during perimenopause or the initial years of menopause,<unk>  carries fewer risks than previously published, and reduces all cause mortality in most scenarios. The American Association of Clinical Endocrinologists (AACE) has also released position statements approving of<unk>  when appropriate. Women receiving this treatment are usually post-, peri-, or surgically menopausal. Menopause is the permanent cessation of menstruation resulting from loss of ovarian follicular activity, defined as beginning twelve months after the final natural menstrual cycle. This twelve month time point divides menopause into early and late transition periods known as 'perimenopause' and 'postmenopause'. Premature menopause can occur if the ovaries are surgically removed, as can be done to treat ovarian or uterine cancer. Demographically, the vast majority of data available is in postmenopausal American women with concurrent pre-existing conditions and an average age of over 60 years. Menopausal symptoms Symptoms of menopause<unk>  is often given as a short-term relief from menopausal symptoms during perimenopause. Potential menopausal symptoms include: * Hot flashes - vasomotor symptoms * Vulvovaginal atrophy - atrophic vaginitis and dryness * Dyspareunia - painful sexual intercourse due to vaginal atrophy and lack of lubrication * Bone loss - decreased bone mineral density, which can eventually lead to osteopenia, osteoporosis, and associated fractures * Decreased sexual desire * Defeminization - diminished feminine fat distribution and accelerated skin aging * Sleep disturbances and joint pain The most common of these are loss of sexual drive and vaginal dryness. Heart disease coronary heart disease with<unk>  vary depending on age and time since menopause. The effect of<unk>  in menopause appears to be divergent, with lower risk of heart disease when started within five years, but no impact after ten. There may be an increase in heart disease if<unk>  is given twenty years post-menopause. This variability has led some reviews to suggest an absence of significant effect on morbidity. Importantly, there is no difference in long-term mortality from<unk> , regardless of age. A Cochrane review suggested that women starting<unk>  less than 10 years after menopause had lower mortality and coronary heart disease, without any strong effect on the risk of stroke and pulmonary embolism. Those starting therapy more than 10 years after menopause showed little effect on mortality and coronary heart disease, but an increased risk of stroke. Both therapies had an association with venous clots and pulmonary embolism.<unk>  with estrogen and progesterone also improves cholesterol levels. With menopause, HDL decreases, while LDL, triglycerides and lipoprotein a increase, patterns that reverse with estrogen. Beyond this,<unk>  improves heart contraction, coronary blood flow, sugar metabolism, and decreases platelet aggregation and plaque formation.<unk>  may promote reverse cholesterol transport through induction of cholesterol ABC transporters.<unk>  also results in a large reduction in the pro-thrombotic lipoprotein a. Studies on cardiovascular disease with testosterone therapy have been mixed, with some suggesting no effect or a mild negative effect, though others have shown an improvement in surrogate markers such as cholesterol, triglycerides and weight. Testosterone has a positive effect on vascular endothelial function and tone with observational studies suggesting that women with lower testosterone may be at greater risk for heart disease. Available studies are limited by small sample size and study design. Low sex hormone binding globulin, which occurs with menopause, is associate with increased body mass index and risk for type 2 diabetes. Blood clots saphenous vein; oral estrogen is associated with increased risk of venous blood clots due to increased liver formation of vitamin K-dependent clotting factors. Effects of<unk>  on venous blood clot formation and potential for pulmonary embolism may vary with different estrogen and progestogen therapies, and with different doses or method of use. Comparisons between routes of administration suggest that when estrogens are applied to the skin or vagina, there is a lower risk of blood clots, whereas when used orally, the risk of blood clots and pulmonary embolism is increased. Skin and vaginal routes of hormone therapy are not subject to first pass metabolism, and so lack the anabolic effects that oral therapy has on liver synthesis of vitamin K-dependent clotting factors, possibly explaining why oral therapy may increase blood clot formation. While a 2018 review found that taking progesterone and estrogen together can decrease this risk, other reviews reported an increased risk of blood clots and pulmonary embolism when estrogen and progestogen were combined, particularly when treatment was started 10 years or more after menopause and when the women were older than 60 years. The risk of venous thromboembolism may be reduced with bioidentical preparations, though research on this is only preliminary. Stroke Multiple studies suggest that the possibility of<unk>  related stroke is absent if therapy is started within five years of menopause, and that the association is absent or even preventive when given by non-oral routes. Ischemic stroke risk was increased during the time of intervention in the WHI, with no significant effect after the cessation of therapy and no difference in mortality at long term follow up. When oral synthetic estrogen or combined estrogen-progestogen treatment is delayed until 5 years from menopause, cohort studies in Swedish women have suggested an association with hemorrhagic and ischemic stroke. Another large cohort of Danish women suggested that the specific route of administration was important, finding that although oral estrogen increased risk of stroke, absorption through the skin had no impact, and vaginal estrogen actually had a decreased risk. Endometrial cancer Endometrial cancer can be associated with<unk> , particularly in those not taking a progestogen. In postmenopausal women, continuous combined estrogen plus progestin decreases endometrial cancer incidence. The duration of progestogen therapy should be at least 14 days per cycle to prevent endometrial disease. Endometrial cancer has been grouped into two forms in the context of hormone replacement. Type 1 is the most common, can be associated with estrogen therapy, and is usually low grade. Type 2 is not related to estrogen stimulation and usually higher grade and poorer in prognosis. The endometrial hyperplasia that leads to endometrial cancer with estrogen therapy can be prevented by concomitant administration of progestogen. The extensive use of high-dose estrogens for birth control in the 1970s is thought to have resulted in a significant increase in the incidence of type 1 endometrial cancer. Paradoxically, progestogens do promote the growth of uterine fibroids, and a pelvic ultrasound can be performed before beginning<unk>  to make sure there are no underlying uterine or endometrial lesions. Androgens do not stimulate endometrial proliferation in post menopausal women, and appear to inhibit the proliferation induced by estrogen to a certain extent. There is insufficient high‐quality evidence to inform women considering<unk>  after treatment for endometrial cancer. Breast cancer Studies regarding the association of breast cancer with hormone replacement are inconsistent and vary with type of replacement and time since menopause. While some evaluations suggest an increased risk, in others it is decreased. This inconsistency of effect has been suggested to imply a lack of meaningful impact of<unk>  on breast cancer risk. There is a non-statistically significant increased rate of breast cancer for<unk>  with synthetic progesterone. The risk may be reduced with bioidentical progesterone, though the only prospective study that suggested this was underpowered due to the rarity of breast cancer in the control population. There have been no randomized controlled trials as of 2018. The relative risk of breast cancer also varies depending on the interval between menopause and<unk>  and route of synthetic progestin administration. The most recent follow up of the Women's Health Inititiative participants demonstrated a lower incidence of breast cancer in post-hysterectomy participants taking equine estrogen alone, though the relative risk was increased if estrogen was taken with medroxy-progesterone. Estrogen is usually only given alone in the setting of a hysterectomy due to the increased risk of vaginal bleeding and uterine cancer with unopposed estrogen.<unk>  has been more strongly associated with risk of breast cancer in women with lower body mass indices (BMIs). No breast cancer association has been found with BMIs of over 25. It has been suggested by some that the absence of significant effect in some of these studies could be due to selective prescription to overweight women who have higher baseline estrone, or to the very low progesterone serum levels after oral administration leading to a high tumor inactivation rate. Evaluating the response of breast tissue density to<unk>  using mammography appears to help assessing the degree of breast cancer risk associated with
Hormone replacement therapy
Antihormone therapy
Hormonal therapy 
Estrogen deprivation therapy
Androgen replacement therapy
Hormone therapy
Feminizing hormone therapy
Masculinizing hormone therapy