119-534: Polydiethylstilbestrol phosphate ( PSP , PDSP ) is an estrogen medication which has been used in scientific research and has been studied for use in veterinary medicine as a livestock growth promoter. It is a phosphate ester of diethylstilbestrol (DES) in the form of a polymer and is a polymeric form of fosfestrol (diethylstilbestrol diphosphate); PDSP acts as a long-lasting prodrug of DES. It has similarities to polyestradiol phosphate and polyestriol phosphate . This drug article relating to
238-468: 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. Estrogen therapy appears to have a beneficial influence on mood in depressed and euthymic perimenopausal women. Conversely, research on combined estrogen and progestogen therapy for depressive symptoms in menopausal women
357-599: A progestagen , gestagen , or gestogen , is a type of medication which produces effects similar to those of the natural female sex hormone progesterone in the body. A progestin is a synthetic progestogen. Progestogens are used most commonly in hormonal birth control and menopausal hormone therapy . They can also be used in the treatment of gynecological conditions , to support fertility and pregnancy , to lower sex hormone levels for various purposes, and for other indications. Progestogens are used alone or in combination with estrogens . They are available in
476-568: A 20- to 45-fold higher risk of VTE relative to non-use. The absolute incidence was about 6%. Conversely, the risk of VTE in transgender women is much lower with oral or transdermal estradiol plus high-dose cyproterone acetate. Ethinylestradiol is thought to have been primarily responsible for the VTE risk, but cyproterone acetate may have contributed as well. Ethinylestradiol is no longer used in transgender hormone therapy, and doses of cyproterone acetate have been reduced. Progestogens may influence
595-502: A ceiling effect such that past a certain low concentration threshold (e.g., approximately 10.2 pg/mL for estradiol), additional estrogens alone may not further increase the risk of breast cancer in postmenopausal women. There are also indications that the fluctuations in estrogen levels across the normal menstrual cycle in premenopausal women may be important for breast cancer risk. In contrast to estrogen-only therapy, combined estrogen and progestogen treatment, although dependent on
714-413: A comparably much higher risk. The increase in risk also differs according to the specific progestogen used. Treatment with estradiol plus medroxyprogesterone acetate ( OR = 1.19), norethisterone acetate ( OR = 1.44), levonorgestrel ( OR = 1.47), or a mixed progestogen subgroup ( OR = 1.99) were all associated with an increased risk. In a previous review, the increase in breast cancer risk
833-1083: A component of hormone therapy for transgender women and transgender men . They are used in transgender women in combination with estrogens to help suppress and block testosterone . Progestogens might also have other beneficial effects in transgender women, but these are controversial and unsupported at present. Examples of progestogens used in hormone therapy for transgender women include cyproterone acetate , medroxyprogesterone acetate , and progesterone . Progestogens, such as medroxyprogesterone and lynestrenol , are used in transgender men to help suppress menses . Progestogens have also been used to delay puberty in transgender boys and girls . Certain progestogens, including megestrol acetate , medroxyprogesterone acetate, cyproterone acetate, and chlormadinone acetate , have been used at high doses to reduce hot flashes in men undergoing androgen deprivation therapy , for instance to treat prostate cancer . Progestogens are used to treat menstrual disorders such as secondary amenorrhea and dysfunctional uterine bleeding . In
952-399: A disappearance of breast nodularity . Progestogens that have been used for such purposes include topical progesterone , dydrogesterone , promegestone , lynestrenol , medroxyprogesterone acetate , dienogest , and medrogestone . Progestogens are used in the treatment of breast hypoplasia and lactation insufficiency . This is because they induce lobuloalveolar development of
1071-852: A high incidence of adverse mood effects with combined birth control pills. However, doses of estrogens and progestogens 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
1190-546: A high oral dose of conjugated estrogens (Premarin alone and with medroxyprogesterone acetate as Prempro ). In a study by the NIH, esterified estrogens were not proven to pose the same risks to health as conjugated estrogens. Menopausal hormone therapy has favorable effects on serum cholesterol levels, and when initiated immediately upon menopause may reduce the incidence of cardiovascular disease, although this hypothesis has yet to be tested in randomized trials. Estrogen appears to have
1309-752: A higher risk of venous thromboembolism (VTE). An exception is medroxyprogesterone acetate as a progestogen-only injectable contraceptive , which has been associated with a 2- to 4-fold increase in risk of VTE relative to other progestogens 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 progestogens 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
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#17328688967051428-399: A higher risk of VTE with oral estrogen and progestogen therapy. Women with thrombophilia have a dramatically higher risk of VTE with estrogen and progestogen therapy than women without thrombophilia. Depending on the condition, risk of VTE can be increased as much as 50-fold in such women relative to non-use. Estrogens induce the production of sex hormone-binding globulin (SHBG) in
1547-841: A history of venous thromboembolism among others. Progestogens have relatively few side effects at typical dosages. Side effects of progestogens 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 progestogens may include an increased risk of breast cancer , cardiovascular disease , and blood clots , among others. Some of
1666-945: A history of at least one spontaneous preterm birth. Progestogens have been used to treat precocious puberty in both boys and girls. They have also been used to delay puberty in transgender youth . Certain progestogens, such as cyproterone acetate and medroxyprogesterone acetate , are used as a form of chemical castration to treat sexual deviance in men, particularly sex offenders . They are specifically used to treat paraphilias and hypersexuality . They work by suppressing gonadal testosterone production and hence circulating testosterone levels. This results in decreased libido and interference with erectile function and ability to attain orgasm . Progestogens are used to treat androgen-dependent skin and hair conditions in women. These include oily skin , acne , seborrhea , hirsutism , scalp hair loss , and hidradenitis suppurativa . They act by suppressing testosterone levels and, in
1785-540: A lesser extent than oral estrogen. Due to its effects on liver protein synthesis, oral estrogen is procoagulant , and has been found to increase the risk of venous thromboembolism (VTE), including of both deep vein thrombosis (DVT) and pulmonary embolism (PE). Conversely, modern oral contraceptives are not associated with an increase in the risk of stroke and myocardial infarction (heart attack) in healthy, non- smoking premenopausal women of any age, except in those with hypertension (high blood pressure). However,
1904-417: 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
2023-501: A newer-generation progestin. For comparison, the absolute risk of VTE is generally estimated as 1 to 5 per 10,000 woman-years for non-use, 5 to 20 per 10,000 woman-years for pregnancy, and 40 to 65 per 10,000 woman-years for the postpartum period. Risk of VTE with estrogen and progestogen therapy is highest at the start of treatment, particularly during the first year, and decreases over time. Older age , higher body weight , lower physical activity , and smoking are all associated with
2142-414: A normal menstrual cycle , declining levels of progesterone trigger menstruation . Progestogens such as norethisterone acetate and medroxyprogesterone acetate may be used to artificially induce progesterone-associated breakthrough bleeding . The progestogen challenge test or progestogen withdrawal test is used to diagnose amenorrhea . Due to the availability of assays to measure estrogen levels, it
2261-488: A number of synthetic AAS, including methyltestosterone , metandienone , normethandrone , and norethandrolone , produce methylestradiol or ethylestradiol as an active metabolite in small quantities, and can produce estrogenic effects as well. A few progestins, specifically the 19-nortestosterone derivatives norethisterone , noretynodrel , and tibolone , metabolize into estrogens (e.g., ethinylestradiol) and can produce estrogenic effects as well. Diethylstilbestrol
2380-495: A protector effect on atherosclerosis: it lowers LDL and triglycerides, it raises HDL levels and has endothelial vasodilatation properties plus an anti-inflammatory component. Research is underway to determine if risks of estrogen supplement use are the same for all methods of delivery. In particular, estrogen applied topically may have a different spectrum of side effects than when administered orally, and transdermal estrogens do not affect clotting as they are absorbed directly into
2499-444: A second-line therapy for this indication. However, they produce various side effects , such as dyspnea , weight gain , vaginal bleeding , nausea , fluid retention , hypertension , thrombophlebitis , and thromboembolic complications . In addition, megestrol acetate has been found to be significantly inferior to aromatase inhibitors in the treatment of breast cancer, and in relation to this, progestogens have been moved down in
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#17328688967052618-563: A significantly greater risk of VTE than pregnane derivatives such as medroxyprogesterone acetate and dydrogesterone and nortestosterone derivatives such as norethisterone and levonorgestrel . However, these findings may just be statistical artifacts. In contrast to progestins, the addition of oral progesterone to either oral or transdermal estrogen therapy is not associated with a higher risk of VTE. However, oral progesterone achieves very low progesterone levels and has relatively weak progestogenic effects, which might be responsible for
2737-417: A significantly increased risk of cardiovascular events such as VTE. However, such risks have been found to vary depending on the type of estrogen and the route of administration. The risk of VTE is increased by approximately 2-fold in women taking oral estrogen for menopausal hormone therapy. However, clinical research to date has generally not distinguished between conjugated estrogens and estradiol. This
2856-399: A small but significant increase in the risk of stroke, though not of myocardial infarction, has been found in menopausal women taking hormone replacement therapy. An increase in the risk of stroke has also been associated with older high-dose oral contraceptives that are no longer used. Menopausal hormone therapy with replacement dosages of estrogens and progestogens has been associated with
2975-680: 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 progestogen-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
3094-475: A variety of coagulation and fibrinolytic factors , including increased factor IX , von Willebrand factor , thrombin–antithrombin complex (TAT), fragment 1+2 , and D-dimer and decreased fibrinogen , factor VII , antithrombin , protein S , protein C , tissue plasminogen activator (t-PA), and plasminogen activator inhibitor-1 (PAI-1). Although this is true for oral estrogen, transdermal estradiol has been found only to reduce PAI-1 and protein S, and to
3213-812: A variety of different forms of hormonal birth control for females, including combined estrogen and progestogen forms like combined oral contraceptive pills , combined contraceptive patches , combined contraceptive vaginal rings , and combined injectable contraceptives ; and progestogen-only forms like progestogen-only contraceptive pills ("mini-pills"), progestogen-only emergency contraceptive pills ("day-after pills"), progestogen-only contraceptive implants , progestogen-only intrauterine devices , progestogen-only contraceptive vaginal rings , and progestogen-only injectable contraceptives . Progestogens mediate their contraceptive effects by multiple mechanisms, including prevention of ovulation via their antigonadotropic effects; thickening of cervical mucus , making
3332-480: A variety of estrogens such as diethylstilbestrol , ethinylestradiol , polyestradiol phosphate , estradiol undecylate , estradiol valerate , and estradiol has been used to treat prostate cancer in men. It is effective because estrogens are functional antiandrogens , capable of suppressing testosterone levels to castrate concentrations and decreasing free testosterone levels by increasing sex hormone-binding globulin (SHBG) production. High-dose estrogen therapy
3451-948: A wide variety of formulations and for use by many different routes of administration . Examples of estrogens include bioidentical estradiol , natural conjugated estrogens , synthetic steroidal estrogens like ethinylestradiol , and synthetic nonsteroidal estrogens like diethylstilbestrol . Estrogens are one of three types of sex hormone agonists , the others being androgens / anabolic steroids like testosterone and progestogens like progesterone . Side effects of estrogens include breast tenderness , breast enlargement , headache , nausea , and edema among others. Other side effects of estrogens include an increased risk of blood clots , cardiovascular disease , and, when combined with most progestogens, breast cancer . In men, estrogens can cause breast development , feminization , infertility , low testosterone levels , and sexual dysfunction among others. Estrogens are agonists of
3570-793: A wide variety of formulations and for use by many different routes of administration . Examples of progestogens include natural or bioidentical progesterone as well as progestins such as medroxyprogesterone acetate and norethisterone . Side effects of progestogens include menstrual irregularities , headaches , nausea , breast tenderness , mood changes, acne , increased hair growth , and changes in liver protein production among others. Other side effects of progestogens may include an increased risk of breast cancer , cardiovascular disease , and blood clots . At high doses, progestogens can cause low sex hormone levels and associated side effects like sexual dysfunction and an increased risk of bone fractures . Progestogens are agonists of
3689-428: Is a nonsteroidal estrogen that is no longer used medically. It is a member of the stilbestrol group. Other stilbestrol estrogens that have been used clinically include benzestrol , dienestrol , dienestrol acetate , diethylstilbestrol dipropionate , fosfestrol , hexestrol , and methestrol dipropionate . Chlorotrianisene , methallenestril , and doisynoestrol are nonsteroidal estrogens structurally distinct from
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3808-641: Is a mixture of natural estrogens including estrone sulfate and equine estrogens such as equilin sulfate and 17β-dihydroequilin sulfate . A related and very similar product to conjugated estrogens, differing from it only in composition, is esterified estrogens . Testosterone , prasterone (dehydroepiandrosterone; DHEA), boldenone (δ -testosterone), and nandrolone (19-nortestosterone) are naturally occurring androgens / anabolic steroids (AAS) which form estradiol as an active metabolite in small amounts and can produce estrogenic effects, most notably gynecomastia in men at sufficiently high dosages. Similarly,
3927-459: Is a more potent synthetic analogue of estradiol that is used widely in hormonal contraceptives . Other synthetic derivatives of estradiol related to ethinylestradiol that are used clinically include mestranol , quinestrol , ethinylestradiol sulfonate , moxestrol , and methylestradiol . Conjugated estrogens (brand name Premarin), an estrogen product manufactured from the urine of pregnant mares and commonly used in menopausal hormone therapy,
4046-561: Is about 0.5 to 2 in 1,000 (0.125%). Aside from type of estrogen and the route of administration, the risk of VTE with oral estrogen is also moderated by other factors, including the concomitant use of a progestogen, dosage, age, and smoking . The combination of oral estrogen and a progestogen has been found to double the risk of VTE relative to oral estrogen alone ( RR Tooltip Relative risk = 2.05 for estrogen monotherapy, and RR Tooltip relative risk = 2.02 for combined estrogen–progestogen therapy in comparison). However, while this
4165-498: Is about 1.5-fold higher with estrogen alone and about 2.5-fold higher with estrogen plus progestogen therapy relative to non-use. The increase in breast cancer risk with estrogen and progestogen therapy was shown to be causal with conjugated estrogens plus medroxyprogesterone acetate in the Women's Health Initiative randomized controlled trials . Breast cancer risk with combined estrogen and progestogen therapy may differ depending on
4284-407: Is also more protective. The increase in risk of endometrial cancer is similarly decreased with continuous estrogen–progestogen therapy ( RR = 0.2–0.7). For these reasons, progestogens are always used alongside estrogens in women who have intact uteruses. Estrogens affect liver protein synthesis and thereby influence the cardiovascular system . They have been found to affect the production of
4403-414: Is also some evidence that estrogens may improve mood and well-being in non-depressed perimenopausal women. Estrogens do not appear to be effective in the treatment of depression in postmenopausal women. This suggests that there is a window of opportunity for effective treatment of depressive symptoms with estrogens. Research on combined estrogen and progestogen therapy for depressive symptoms in
4522-402: 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 ,
4641-637: Is associated with poor tolerability and safety, namely gynecomastia and cardiovascular complications such as thrombosis . For this reason, has largely been replaced by newer antiandrogens such as gonadotropin-releasing hormone analogues and nonsteroidal antiandrogens . It is still sometimes used in the treatment of prostate cancer however, and newer estrogens with atypical profiles such as GTx-758 that have improved tolerability profiles are being studied for possible application in prostate cancer. High-dose estrogen therapy with potent synthetic estrogens such as diethylstilbestrol and ethinylestradiol
4760-717: Is because they suppress growth hormone -induced insulin-like growth factor 1 (IGF-1) production in the liver . High-dose estrogen therapy has been used successfully in the treatment of sexual deviance such as paraphilias in men. However, it has been found to produce many side effects (e.g., gynecomastia , feminization , cardiovascular disease , blood clots ), and so is no longer recommended for such purposes. High-dose estrogen therapy works by suppressing testosterone levels, similarly to high-dose progestogen therapy and gonadotropin-releasing hormone (GnRH) modulator therapy. Lower dosages of estrogens have also been used in combination with high-dose progestogen therapy in
4879-730: Is currently under development for medical indications, but has not yet been approved in any country. A variety of synthetic estrogen esters , such as estradiol valerate , estradiol cypionate , estradiol acetate , estradiol benzoate , estradiol undecylate , and polyestradiol phosphate , are used clinically. The aforementioned compounds behave as prodrugs to estradiol, and are much longer-lasting in comparison when administered by intramuscular or subcutaneous injection. Esters of estrone and estriol also exist and are or have been used in clinical medicine, for example estrone sulfate (e.g., as estropipate ), estriol succinate , and estriol glucuronide (as Emmenin and Progynon ). Ethinylestradiol
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4998-561: Is effective in the treatment of breast cancer as well and has about the same degree of effectiveness as antiestrogen therapy, although it is far less commonly used due to adverse effects. The usefulness of high-dose estrogen therapy in the treatment of ER-positive breast cancer is attributed to a bimodal effect in which high concentrations of estrogens signal breast cancer cells to undergo apoptosis , in contrast to lower concentrations of estrogens which stimulate their growth. A 2017 systematic review and meta-analysis of 14 studies assessed
5117-603: Is greatly increased by 6 months of treatment ( OR Tooltip odds ratio = 5.4) and further increased after 36 months of treatment ( OR = 16.0). This can eventually progress to endometrial cancer, and the risk of endometrial cancer similarly increases with duration of treatment (less than one year, RR Tooltip relative risk = 1.4; many years (e.g., more than 10 years), RR = 15.0). The risk of endometrial cancer also stays significantly elevated many years after stopping unopposed estrogen therapy, even after 15 years or more ( RR = 5.8). Progestogens prevent
5236-608: Is lacking for a sustained increase in breast size with estrogens. Published 2019 and 2020 guidelines from the North American Menopause Society (NAMS) and European Menopause and Andropause Society (EMAS) have reviewed the topic of estrogen therapy for depressive symptoms in the peri- and postmenopause . There is some evidence that estrogens are effective in the treatment of depression in perimenopausal women. The magnitude of benefit appears to be similar to that of classical antidepressants . There
5355-466: Is much more resistant to hepatic metabolism, with a mean oral bioavailability of approximately 45%, and the transdermal route has a similar impact on hepatic protein synthesis as the oral route. Conjugated estrogens are also more resistant to hepatic metabolism than estradiol and show disproportionate effects on hepatic protein production as well, although not to the same magnitude as ethinylestradiol. These differences are considered to be responsible for
5474-432: Is needed to clarify this issue. In contrast to oral estrogens as a group, transdermal estradiol at typical menopausal replacement dosages has not been found to increase the risk of VTE or other cardiovascular events. Both combined birth control pills (which contain ethinylestradiol and a progestin) and pregnancy are associated with about a 4-fold increase in risk of VTE, with the risk increase being slightly greater with
5593-546: 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
5712-417: Is now rarely used. Progestogens are used in the prevention and treatment of uterine disorders such as endometrial hyperplasia , endometriosis , uterine fibroids , and uterine hypoplasia . Progestogens are used to treat benign breast disorders . They are associated not only with a reduction in breast pain , but also a decrease in breast cell proliferation , a decrease in breast gland size, and
5831-555: Is of importance because conjugated estrogens have been found to be more resistant to hepatic metabolism than estradiol and to increase clotting factors to a greater extent. Only a few clinical studies have compared oral conjugated estrogens and oral estradiol. Oral conjugated estrogens have been found to possess a significantly greater risk of thromboembolic and cardiovascular complications than oral estradiol ( OR Tooltip Odds ratio = 2.08) and oral esterified estrogens ( OR Tooltip Odds ratio = 1.78). However, in another study,
5950-546: Is scarce and inconclusive. Some researchers contend that progestogens have an adverse influence on mood and reduce the benefits of estrogens on mood, whereas other researchers maintain that progestogens 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. In most women, sexual desire
6069-595: Is similar to the increase that occurs during pregnancy. Conversely, increases in SHBG levels are much lower with estradiol, especially when it is used parenterally. Estradiol-containing combined birth control pills , like estradiol valerate/dienogest and estradiol/nomegestrol acetate , and high-dose parenteral polyestradiol phosphate therapy have both been found to increase SHBG levels by about 1.5-fold. Hormone therapy with high-dose ethinylestradiol and cyproterone acetate in transgender women has been associated with
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#17328688967056188-456: Is similar to the increase that occurs during pregnancy. Conversely, increases in SHBG levels are much lower with estradiol, especially when used parenterally. High-dose parenteral polyestradiol phosphate therapy has been found to increase SHBG levels by about 1.5-fold. Estrogens are responsible for breast development and, in relation to this, are strongly implicated in the development of breast cancer . In addition, estrogens stimulate
6307-803: 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 . However, although this has been apparent in retrospective cohort and nested case–control studies , no greater risk of VTE has been observed in prospective cohort and case–control studies . These kinds of observational studies have certain advantages over
6426-580: Is true for most progestogens, there appears to be no increase in VTE risk relative to oral estrogen alone with the addition of oral progesterone or the atypical progestin dydrogesterone . The dosage of oral estrogen appears to be important for VTE risk, as 1 mg/day oral estradiol increased VTE incidence by 2.2-fold while 2 mg/day oral estradiol increased VTE incidence by 4.5-fold (both in combination with norethisterone acetate). The risk of VTE and other cardiovascular complications with oral estrogen–progestogen therapy increases dramatically with age. In
6545-423: 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. 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
6664-446: Is without severe lesions . Approximately 95% of orally ingested estradiol is inactivated during first-pass metabolism. Nonetheless, levels of estradiol in the liver with oral administration are supraphysiological and approximately 4- to 5-fold higher than in circulation due to the first-pass. This does not occur with parenteral routes of estradiol, such as transdermal, vaginal, or injection. In contrast to estradiol, ethinylestradiol
6783-404: The breasts , which is required for lactation and breastfeeding . Progestogens have been used at high doses to treat benign prostatic hyperplasia (BPH). They act by suppressing gonadal testosterone production and hence circulating testosterone levels. Androgens like testosterone stimulate the growth of the prostate gland . Progestogens were first found to be effective at high doses in
6902-725: The cervix largely impenetrable to sperm ; preventing capacitation of sperm due to changes in cervical fluid, thereby making sperm unable to penetrate the ovum ; and atrophic changes in the endometrium , making the endometrium unsuitable for implantation . They may also decrease tubal motility and ciliary action. Progestogens are used in combination with estrogens in menopausal hormone therapy in women. They are also used in combination with estrogens in hormone therapy for hypogonadism and delayed puberty in girls and women. They are used mainly to prevent endometrial hyperplasia and increased risk of endometrial cancer from unopposed estrogen therapy. Progestogens are used as
7021-574: The endometrium , and this underlies their use in menopausal hormone therapy. Progesterone was first introduced for medical use in 1934 and the first progestin, ethisterone , was introduced for medical use in 1939. More potent progestins, such as norethisterone , were developed and started to be used in birth control in the 1950s. Around 60 progestins have been marketed for clinical use in humans or use in veterinary medicine . These progestins can be grouped into different classes and generations. Progestogens are available widely throughout
7140-712: The estrogen receptors , the biological targets of endogenous estrogens like estradiol . They have important effects in many tissues in the body, including in the female reproductive system ( uterus , vagina , and ovaries ), the breasts , bone , fat , the liver , and the brain among others. Unlike other medications like progestins and anabolic steroids, estrogens do not have other hormonal activities. Estrogens also have antigonadotropic effects and at sufficiently high dosages can strongly suppress sex hormone production. Estrogens mediate their contraceptive effects in combination with progestins by inhibiting ovulation . Estrogens were first introduced for medical use in
7259-556: The genito-urinary system is a stub . You can help Misplaced Pages by expanding it . Estrogen (medication) An estrogen ( E ) is a type of medication which is used most commonly in hormonal birth control and menopausal hormone therapy , and as part of feminizing hormone therapy for transgender women . They can also be used in the treatment of hormone-sensitive cancers like breast cancer and prostate cancer and for various other indications. Estrogens are used alone or in combination with progestogens . They are available in
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#17328688967057378-551: The intestines , liver , and uterus relative to estradiol. Besides oral contraceptives, other forms of combined hormonal contraception include contraceptive patches , contraceptive vaginal rings , and combined injectable contraceptives . Contraceptive patches and vaginal rings contain ethinylestradiol as the estrogen component, while combined injectable contraceptives contain estradiol or more typically an estradiol ester . Estrogen and other hormones are given to postmenopausal women in order to prevent osteoporosis as well as treat
7497-408: 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 progestogens 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
7616-468: The liver and hepatic protein synthesis than natural estrogens. This is related to the fact that synthetic estrogens like ethinylestradiol are much more resistant to metabolism in the liver than natural estrogens. Unopposed estrogen therapy stimulates the growth of the endometrium and is associated with a dramatically increased risk of endometrial hyperplasia and endometrial cancer in postmenopausal women. The risk of endometrial hyperplasia
7735-416: 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). Progestogens when used by themselves at typical clinical dosages, for instance in progestogen-only birth control , do not affect coagulation and are not generally associated with
7854-738: The progesterone receptors (PRs) and produce progestogenic , or progestational , effects. They have important effects in the female reproductive system ( uterus , cervix , and vagina ), the breasts , and the brain . In addition, many progestogens also have other hormonal activities, such as androgenic , antiandrogenic , estrogenic , glucocorticoid , or antimineralocorticoid activity. They also have antigonadotropic effects and at high doses can strongly suppress sex hormone production. Progestogens mediate their contraceptive effects both by inhibiting ovulation and by thickening cervical mucus , thereby preventing fertilization . They have functional antiestrogenic effects in certain tissues like
7973-535: The stilbestrols diethylstilbestrol , hexestrol , and dienestrol , are no longer used in menopausal hormone therapy, owing to their disproportionate effects on liver protein synthesis and associated health risks. Estrogens are used along with progestogens to treat hypogonadism and delayed puberty in women. Estrogens are used along with antiandrogens and progestogens as a component of feminizing hormone therapy for transgender women and other transfeminine individuals . High-dose estrogen therapy with
8092-533: The absence of increase in VTE risk. Parenteral progesterone, such as vaginal or injectable progesterone, which can achieve luteal-phase levels of progesterone and associated progestogenic effects, has not been characterized in terms of VTE risk. A 2012 meta-analysis estimated that the absolute risk of VTE is 2 per 10,000 women for non-use, 8 per 10,000 women for ethinylestradiol and levonorgestrel-containing birth control pills, and 10 to 15 per 10,000 women for birth control pills containing ethinylestradiol and
8211-521: The aforementioned types of studies, such as better ability to control for confounding factors like new-user bias. As such, it is unclear whether the higher risk of VTE with newer-generation birth control pills is a real finding or a statistical artifact. Androgenic progestins have been found to antagonize to some degree the effect of estrogens on coagulation. First-generation progestins are more androgenic, while newer-generation progestins are weakly androgenic or antiandrogenic, and this might explain
8330-647: The cardiovascular health effects of progestogens, but more research is needed similarly. Estrogen alone, progestogen alone, and combined estrogen and progestogen therapy are all associated with increased risks of breast cancer when used in menopausal hormone therapy for peri- and postmenopausal women relative to non-use. These risks are higher for combined estrogen and progestogen therapy than with estrogen alone or progestogen alone. In addition to breast cancer risk, estrogen alone and estrogen plus progestogen therapy are associated with higher breast cancer mortality . With 20 years of use, breast cancer incidence
8449-717: The case of antiandrogenic progestogens, by directly blocking the actions of androgens. Progestogens are used to treat hyperandrogenism , such as due to polycystic ovary syndrome and congenital adrenal hyperplasia , in women. Examples include cyproterone acetate and chlormadinone acetate . Certain progestins can be used at very high doses to increase appetite in conditions like cachexia , anorexia , and wasting syndromes . In general, they are used in combination with certain other steroid medications such as dexamethasone . Their effects take several weeks to become apparent, but are relatively long-lived when compared to those of corticosteroids . Furthermore, they are recognized as being
8568-409: The early 1930s. They started to be used in birth control in combination with progestins in the 1950s. A variety of different estrogens have been marketed for clinical use in humans or use in veterinary medicine , although only a handful of these are widely used. These medications can be grouped into different types based on origin and chemical structure . Estrogens are available widely throughout
8687-445: The effects of estrogens on the endometrium. As a result, they are able to completely block the increase in risk of endometrial hyperplasia caused by estrogen therapy in postmenopausal women, and are even able to decrease it below baseline ( OR = 0.3 with continuous estrogen–progestogen therapy). Continuous estrogen–progestogen therapy is more protective than sequential therapy, and a longer duration of treatment with continuous therapy
8806-419: The estrogen component, but a few contain estradiol or estradiol valerate. Ethinylestradiol is generally used in oral contraceptives instead of estradiol because it has superior oral pharmacokinetics (higher bioavailability and less interindividual variability ) and controls vaginal bleeding more effectively. This is due to its synthetic nature and its resistance to metabolism in certain tissues such as
8925-583: The greater risk of cardiovascular events with ethinylestradiol and conjugated estrogens relative to estradiol. High-dosage oral synthetic estrogens like diethylstilbestrol and ethinylestradiol are associated with fairly high rates of severe cardiovascular complications. Diethylstilbestrol has been associated with an up to 35% risk of cardiovascular toxicity and death and a 15% incidence of VTE in men treated with it for prostate cancer. In contrast to oral synthetic estrogens, high-dosage polyestradiol phosphate and transdermal estradiol have not been found to increase
9044-505: The growth and accelerate the progression of ER-positive breast cancer . In accordance, antiestrogens like the selective estrogen receptor modulator (SERM) tamoxifen , the ER antagonist fulvestrant , and the aromatase inhibitors (AIs) anastrozole and exemestane are all effective in the treatment of ER-positive breast cancer. Antiestrogens are also effective in the prevention of breast cancer. Paradoxically, high-dose estrogen therapy
9163-539: The growth of prostate tumors . Progestogens are used in fertility medicine for women. For example, progesterone (or sometimes dydrogesterone or hydroxyprogesterone caproate ) is used for luteal support in in-vitro fertilization protocols. Certain progestogens are used to support pregnancy , including progesterone , hydroxyprogesterone caproate , dydrogesterone , and allylestrenol . They are used questionably for treatment of recurrent pregnancy loss and for prevention of preterm birth in pregnant women with
9282-876: The hepatic production of coagulant and fibrinolytic factors and increase the risk of VTE and sometimes stroke, they also influence the liver synthesis of blood lipids and can have beneficial effects on the cardiovascular system. With oral estradiol, there are increases in circulating triglycerides , HDL cholesterol , apolipoprotein A1 , and apolipoprotein A2 , and decreases in total cholesterol , LDL cholesterol , apolipoprotein B , and lipoprotein(a) . Transdermal estradiol has less-pronounced effects on these proteins and, in contrast to oral estradiol, reduces triglycerides. Through these effects, both oral and transdermal estrogens can protect against atherosclerosis and coronary heart disease in menopausal women with intact arterial endothelium that
9401-508: The increase in VTE risk has ranged from 3- to 5-fold. The incidence of VTE in studies with very-high-dose progestogen 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. In contrast to progestogen-only birth control, the addition of progestins to oral estrogen therapy, including in combined birth control pills and menopausal hormone therapy ,
9520-720: The increase in VTE risk with 0.625 mg/day oral conjugated estrogens plus medroxyprogesterone acetate and 1 or 2 mg/day oral estradiol plus norethisterone acetate was found to be equivalent ( RR Tooltip Relative risk = 4.0 and 3.9, respectively). Other studies have found oral estradiol to be associated with an increase in risk of VTE similarly ( RR Tooltip Relative risk = 3.5 in one, OR Tooltip odds ratio = 3.54 in first year of use in another). As of present, there are no randomized controlled trials comparing oral conjugated estrogens and oral estradiol in terms of thromboembolic and cardiovascular risks that would allow for unambiguous conclusions, and additional research
9639-643: The issue of estrogen therapy for depressive symptoms associated with menopause . Estrogens appear to be useful in the treatment of schizophrenia in both women and men. Systemic estrogen therapy at adequate doses is effective for and has been used in the treatment of acne in both females and males, but causes major side effects such as feminization and gynecomastia in males. Estrogens that have been marketed come in two major types, steroidal estrogens and nonsteroidal estrogens . Estradiol , estrone , and estriol have all been approved as pharmaceutical drugs and are used medically. Estetrol
9758-897: The latter ( OR = 4.03 and 4.24, respectively). The risk of VTE during the postpartum period is 5-fold higher than during pregnancy. Other research has found that the rate of VTE is 1 to 5 in 10,000 woman-years in women who are not pregnant or taking a birth control pill, 3 to 9 in 10,000 woman-years in women who are on a birth control pill, 5 to 20 in 10,000 women-years in pregnant women, and 40 to 65 in 10,000 women-years in postpartum women. For birth control pills, VTE risk with high doses of ethinylestradiol (>50 μg, e.g., 100 to 150 μg) has been reported to be approximately twice that of low doses of ethinylestradiol (e.g., 20 to 50 μg). As such, high doses of ethinylestradiol are no longer used in combined oral contraceptives, and all modern combined oral contraceptives contain 50 μg ethinylestradiol or less. The absolute risk of VTE in pregnancy
9877-584: The latter. High-dose estrogen therapy was the standard of care for the palliative treatment of breast cancer in women up to the late 1970s or early 1980s. Estrogens may be used in treatment of infertility in women when there is a need to develop sperm -friendly cervical mucus or an appropriate uterine lining . Estrogens like diethylstilbestrol were formerly used in high doses to help support pregnancy . However, subsequent research showed diethylstilbestrol to be ineffective as well as harmful. Estrogens can be used to suppress lactation , for instance in
9996-477: The liver. As such, SHBG levels indicate hepatic estrogenic exposure and may be a reliable surrogate marker for coagulation and VTE risk with estrogen therapy. Combined birth control pills containing different progestins result in SHBG levels that are increased 1.5- to 2-fold with levonorgestrel, 2.5- to 4-fold with desogestrel and gestodene, 3.5- to 4-fold with drospirenone and dienogest , and 4- to 5-fold with cyproterone acetate. SHBG levels differ depending on
10115-548: The observed differences in risk of VTE. The type of estrogen also influences VTE risk. Birth control pills containing estradiol valerate are associated with about half the VTE risk of birth control pills with ethinylestradiol. The type of progestogen in combined menopausal hormone therapy may also modulate VTE risk. Oral estrogens plus dydrogesterone appears to have lower VTE risk relative to inclusion of other progestins. Norpregnane derivatives such as nomegestrol acetate and promegestone have been associated with
10234-523: The only medications to increase lean body mass . Megestrol acetate is the lead drug of this class for the management of cachexia, and medroxyprogesterone acetate is also used. The mechanism of action of the appetite-related effects of these two medications is unknown and may not be related to their progestogenic activity. Very high doses of other progestogens, like cyproterone acetate , have minimal or no influence on appetite and weight. Contraindications of progestogens may include breast cancer and
10353-877: The oral conjugated estrogens and medroxyprogesterone acetate arm of the WHI, the risks of VTE stratified by age were as follows: age 50 to 59, RR = 2.27; age 60 to 69, RR = 4.28; and age 70 to 79, RR = 7.46. Conversely, in the oral conjugated estrogens monotherapy arm of the WHI, the risk of VTE increased with age similarly but was much lower: age 50 to 59, RR = 1.22; age 60 to 69, RR = 1.3; and age 70 to 79, RR = 1.44. In addition to menopausal hormone therapy, cardiovascular mortality has been found to increase considerably with age in women taking ethinylestradiol-containing combined oral contraceptives and in pregnant women. In addition, smoking has been found to exponentially increase cardiovascular mortality in conjunction with combined oral contraceptive use and older age. Whereas
10472-621: The overall evidence showed no association between progestogen-only birth control and depression. The progestins assessed included depot medroxyprogesterone acetate , levonorgestrel -containing contraceptive implants and intrauterine devices , and progestogen-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
10591-516: The peri- and postmenopause is scarce and inconclusive. Estrogens may augment the mood benefits of antidepressants in middle-aged and older women. Menopausal hormone therapy is not currently approved for the treatment of depressive symptoms in the peri- or postmenopause in either the United States or the United Kingdom due to insufficient evidence of effectiveness. More research is needed on
10710-423: The progestin because androgenic progestins oppose the effect of ethinylestradiol on hepatic SHBG production as with its procoagulatory effects. Contraceptive vaginal rings and contraceptive patches likewise have been found to increase SHBG levels by 2.5-fold and 3.5-fold, respectively. Birth control pills containing high doses of ethinylestradiol (>50 μg) can increase SHBG levels by 5- to 10-fold, which
10829-429: The progestogen used, is associated with an increased risk of breast cancer. The increase in risk is dependent on the duration of treatment, with more than five years ( OR = 2.43) having a significantly greater risk than less than five years ( OR = 1.49). In addition, sequential estrogen–progestogen treatment ( OR = 1.76) is associated with a lower risk increase than continuous treatment ( OR = 2.90), which has
10948-494: The progestogen used. Progestins including chlormadinone acetate , cyproterone acetate , medrogestone , medroxyprogesterone acetate , nomegestrol acetate , norethisterone acetate , promegestone , and tibolone have all been associated with similarly increased risk of breast cancer. Some research has found that oral progesterone and dydrogesterone with short-term use (<5 years) may be associated with lower risk of breast cancer relative to other progestins. In
11067-412: The related progestin chlormadinone acetate (10 mg/day for 18–20 days/cycle), though based on limited data. Very-high-dose progestogen 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,
11186-618: The risk of breast cancer in perimenopausal and postmenopausal women treated with estrogens for menopausal symptoms. They found that treatment with estradiol only is not associated with an increased risk of breast cancer ( OR Tooltip odds ratio = 0.90 in RCTs Tooltip randomized controlled trials and OR = 1.11 in observational studies ). This was in accordance with a previous analysis of estrogen-only treatment with estradiol or conjugated estrogens which similarly found no increased risk ( RR = 0.99). Moreover, another study found that
11305-417: The risk of cardiovascular disease in women. In the women's Health Initiative (WHI), the risk of coronary heart disease was greater with the combination of estrogen plus a progestin (specifically medroxyprogesterone acetate ) than with estrogen alone. However, progestogens have varying activities and may differ in terms of cardiovascular risk. A 2015 Cochrane review provided strong evidence that
11424-473: The risk of mood changes and depression with progestogens in hormonal birth control is limited. As of 2019, there is no consistent evidence for adverse effects on mood of hormonal birth control, including progestogen-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
11543-497: The risk of breast cancer with estradiol and conjugated estrogens was not significantly different ( RR = 1.15 for conjugated estrogens versus estradiol). These findings are paradoxical because oophorectomy in premenopausal women and antiestrogen therapy in postmenopausal women are well-established as considerably reducing the risk of breast cancer ( RR = 0.208 to 0.708 for chemoprevention with antiestrogens in postmenopausal women). However, there are indications that there may be
11662-561: The risk of cardiovascular death is 0.06 per 100,000 in women who are age 15 to 34 years, are taking a combined oral contraceptive, and do not smoke, this increases by 50-fold to 3.0 per 100,000 in women who are age 35 to 44 years, are taking a combined oral contraceptive, and do not smoke. Moreover, in women who do smoke, the risk of cardiovascular death in these two groups increases to 1.73 per 100,000 (29-fold higher relative to non-smokers) and 19.4 per 100,000 (6.5-fold higher relative to non-smokers), respectively. Although estrogens influence
11781-1044: The risk of cardiovascular mortality or thromboembolism in men with prostate cancer, although significantly increased cardiovascular morbidity (due mainly to an increase in non-fatal ischemic heart events and heart decompensation ) has been observed with polyestradiol phosphate. Sex hormone-binding globulin (SHBG) levels indicate hepatic estrogenic exposure and may be a surrogate marker for coagulation and VTE risk with estrogen therapy, although this topic has been debated. SHBG levels with birth control pills containing different progestins are increased by 1.5 to 2-fold with levonorgestrel , 2.5- to 4-fold with desogestrel and gestodene , 3.5- to 4-fold with drospirenone and dienogest , and 4- to 5-fold with cyproterone acetate . Contraceptive vaginal rings and contraceptive patches likewise have been found to increase SHBG levels by 2.5-fold and 3.5-fold, respectively. Birth control pills containing high doses of ethinylestradiol (>50 μg) can increase SHBG levels by 5- to 10-fold, which
11900-405: The risk of uncommon or rare but potentially serious issues including endometrial hyperplasia , endometrial cancer , cardiovascular complications (e.g., blood clots , stroke , heart attack ), cholestatic hepatotoxicity , gallbladder disease (e.g., gallstones ), hyperprolactinemia , prolactinoma , and dementia . These adverse effects are moderated by the concomitant use of a progestogen ,
12019-428: The sequential therapy of the disease. Megestrol acetate is the only Food and Drug Administration -approved progestogen for breast cancer. The mechanism of action of progestogens in the treatment of breast cancer is unknown, but may be related to their functional antiestrogenic and/or antigonadotropic effects. Certain progestogens, particularly those with antiandrogenic properties, have been used at high doses in
12138-645: The side effects of progestogens are due not to their progestogenic activity but rather due to off-target activities (e.g., androgenic activity, glucocorticoid activity, antimineralocorticoid activity). At high doses, due to their antigonadotropic effects, progestogens 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. The available evidence on
12257-504: The specific dangers of conjugated estrogens were well understood, standard therapy was 0.625 mg/day of conjugated estrogens (such as Premarin). There are, however, risks associated with conjugated estrogen therapy. Among the older postmenopausal women studied as part of the Women's Health Initiative (WHI), an orally administered conjugated estrogen supplement was found to be associated with an increased risk of dangerous blood clotting . The WHI studies used one type of estrogen supplement,
12376-844: The stilbestrols that have also been used clinically. While used widely in the past, nonsteroidal estrogens have mostly been discontinued and are now rarely if ever used medically. Estrogens have various contraindications . An example is history of thromboembolism (blood clots). The most common side effects of estrogens in general include breast tenderness , breast enlargement , headache , nausea , fluid retention , and edema . In women, estrogens can additionally cause vaginal bleeding , vaginal discharge , and anovulation , whereas in men, estrogens can additionally cause gynecomastia (male breast development ), feminization , demasculinization , sexual dysfunction ( reduced libido and erectile dysfunction ), hypogonadism , testicular atrophy , and infertility . Estrogens can or may increase
12495-406: The symptoms of menopause such as hot flashes, vaginal dryness, urinary stress incontinence, chilly sensations, dizziness, fatigue, irritability, and sweating. Fractures of the spine, wrist, and hips decrease by 50 to 70% and spinal bone density increases by approximately 5% in those women treated with estrogen within 3 years of the onset of menopause and for 5 to 10 years thereafter. Before
12614-647: The systemic circulation, avoiding first-pass metabolism in the liver. This route of administration is thus preferred in women with a history of thromboembolic disease . Estrogen is also used in the therapy of vaginal atrophy, hypoestrogenism (as a result of hypogonadism, oophorectomy , or primary ovarian failure), amenorrhea, dysmenorrhea, and oligomenorrhea. Estrogens can also be used to suppress lactation after child birth. Synthetic estrogens, such as 17α-substituted estrogens like ethinylestradiol and its C3 esters and ethers mestranol , quinestrol , and ethinylestradiol sulfonate , and nonsteroidal estrogens like
12733-513: The treatment of breast engorgement or galactorrhea . However, high doses are needed, the effectiveness is uncertain, and high doses of estrogens in the postpartum period can increase the risk of blood clots . Estrogen has been used to induce growth attenuation in tall girls. Estrogen-induced growth attenuation was used as part of the controversial Ashley Treatment to keep a developmentally disabled girl from growing to adult size. Estrogens have been used to treat acromegaly . This
12852-482: The treatment of endometrial hyperplasia and endometrial cancer in 1959. Subsequently, high-dose gestonorone caproate , hydroxyprogesterone caproate , medroxyprogesterone acetate , and megestrol acetate were approved for the treatment of endometrial cancer. Progestogens, such as megestrol acetate and medroxyprogesterone acetate, are effective at high doses in the treatment of advanced postmenopausal breast cancer . They have been extensively evaluated as
12971-445: The treatment of prostate cancer . These include cyproterone acetate , chlormadinone acetate , and megestrol acetate . Other progestogens such as medroxyprogesterone acetate , hydroxyprogesterone caproate , and gestonorone caproate have also been studied, but have inadequate effectiveness. They act by suppressing gonadal testosterone production and hence circulating testosterone levels. Androgens like testosterone stimulate
13090-623: 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,
13209-621: The treatment of post-menopausal women with hormone therapy for cardiovascular disease had little if any effect and increased the risk of stroke and venous thromboembolic events. It is thought that androgenic progestins like medroxyprogesterone acetate and norethisterone may antagonize the beneficial effects of estrogens on biomarkers of cardiovascular health (e.g., favorable lipid profile changes). However, these findings are mixed and controversial. Differences of progestogens on cardiovascular health and risk have been reviewed and summarized: Route of administration might also influence
13328-590: The treatment of sexual deviance in men. High incidence of sexual dysfunction has similarly been associated with high-dose estrogen therapy in men treated with it for prostate cancer . Estrogens are involved in breast development and may be used as a form of hormonal breast enhancement to increase the size of the breasts . However, acute or temporary breast enlargement is a well-known side effect of estrogens, and increases in breast size tend to regress following discontinuation of treatment. Aside from those without prior established breast development, evidence
13447-897: The type of progestogen used, and the dosage and route of estrogen used. Around half of women with epilepsy who menstruate have a lowered seizure threshold around ovulation , most likely from the heightened estrogen levels at that time. This results in an increased risk of seizures in these women. High doses of synthetic estrogens like ethinylestradiol and diethylstilbestrol can produce prominent untoward side effects like nausea , vomiting , headache , malaise , and dizziness , among others. Conversely, natural estrogens like estradiol and conjugated estrogens are rarely associated with such effects. The preceding side effects of synthetic estrogens do not appear to occur in pregnant women, who already have very high estrogen levels. This suggests that these effects are due to estrogenic activity. Synthetic estrogens have markedly stronger effects on
13566-605: The world and are used in all forms of hormonal birth control and in most menopausal hormone therapy regimens. Progestogens are available in many different forms for use by many different routes of administration . These include oral tablets and capsules , oil and aqueous solutions and suspensions for intramuscular or subcutaneous injection , and various others (e.g., transdermal patches , vaginal rings , intrauterine devices , subcutaneous implants ). Dozens of different progestogens have been marketed for clinical and/or veterinary use. Progestogens are used in
13685-562: The world and are used in most forms of hormonal birth control and in all menopausal hormone therapy regimens. Estrogens have contraceptive effects and are used in combination with progestins ( synthetic progestogens ) in birth control to prevent pregnancy in women. This is referred to as combined hormonal contraception . The contraceptive effects of estrogens are mediated by their antigonadotropic effects and hence by inhibition of ovulation . Most combined oral contraceptives contain ethinylestradiol or its prodrug mestranol as
13804-486: Was found to not be significantly different between these three progestogens. Conversely, there is no significant increase in risk of breast cancer with bioidentical progesterone ( OR = 1.00) or with the atypical progestin dydrogesterone ( OR = 1.10). In accordance, another study found similarly that the risk of breast cancer was not significantly increased with estrogen–progesterone ( RR Tooltip relative risk = 1.00) or estrogen–dydrogesterone ( RR = 1.16) but
13923-445: Was increased for estrogen combined with other progestins ( RR = 1.69). These progestins included chlormadinone acetate , cyproterone acetate , medrogestone , medroxyprogesterone acetate , nomegestrol acetate , norethisterone acetate , and promegestone , with the associations for breast cancer risk not differing significantly between the different progestins in this group. Progestin A progestogen , also referred to as
14042-405: 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 progestogen-only injectable birth control , and recommended caution on the use of progestogen-only birth control in the postpartum period. Studies suggest
14161-416: Was used in the past in the palliation treatment of breast cancer . Its effectiveness is approximately equivalent to that of antiestrogen therapy with selective estrogen receptor modulators (SERMs) like tamoxifen and aromatase inhibitors like anastrozole . The use of high-dose estrogen therapy in breast cancer has mostly been superseded by antiestrogen therapy due to the improved safety profile of
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