Estrogen Deficiency

Also known as: Hypoestrogenism / Oestrogen deficiency

DrugDrug NameDrug Description
DB00286Conjugated estrogensThe conjugated estrogens are noncrystalline mixtures of purified female sex hormones obtained either by its isolation from the urine of pregnant mares or by synthetic generation from vegetal material. Both of these products are later conjugated to natrium sulfate by ester bonds in order to make them more water soluble.[L5605, T475] The conjugated estrogen product contains a mix of estrogen from which about 50% is represented by estrone sulfate followed by 25% of equilin sulfate, 15% of 17-alpha-dehydroequilenin sulfate, 3% of equilenin sulfate, 5% of 17-alpha and 17-beta-dihydroequilenin sulfate, 2% of 17-alpha-estradiolsulfate and 3% of 17-beta-estradiolsulfate. It also presents a large number of unidentified molecules with weak estrogenic activity as well as non-human molecules when it is obtained from pregnant mares urine.[T475] The conjugated estrogen mixture was approved for marketing in US in 1942 based on the efficacy against certain conditions. However, until 1986 official clinical trials were performed and this product was determined to be effective for the treatment of osteoporosis.[T484] The currently approved product of conjugated estrogens was developed by Wyeth Ayerst and FDA approved in 2003.[L5608]
DB01395DrospirenoneDrospirenone is a synthetic progestin commonly found in the popular oral contraceptive, Yaz in combination with [Ethinyl estradiol].[L7973] Aside from its contraceptive effects, drospirenone is used with estrogens to control acne and premenstrual dysphoric disorder (PMDD). Drospirenone has been the subject of widespread safety concern due to the possibility of an increased risk of venous thromboembolism associated with its use.[A182543,A182552] In 2012, however, a safety statement by the FDA concluded that the increase in the risk of thromboembolism resulting from the use of drospirenone remains unclear, as studies regarding this risk are conflicting. Some studies have demonstrated a significantly increased risk and some demonstrating no risk of thromboembolic events. In its statement, the FDA has mentioned that increased risk of venous thromboembolism with oral contraceptives such as drospirenone exists but remains lower than the risk of this condition during pregnancy and during the postpartum period, and this should be considered when assessing potential risks of hormonal contraceptive use.[L7979]
DB00783EstradiolEstradiol (also known as E2 or 17β-estradiol) is a naturally occurring hormone that circulates endogenously within the human body. It is the most potent form of mammalian estrogenic steroids and acts as the major female sex hormone. As such, estradiol plays an essential role in the regulation of the menstrual cycle, in the development of puberty and secondary female sex characteristics, as well as in ageing and several hormonally-mediated disease states. Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects [A31620]. Estradiol is commercially available in several hormone therapy products for managing conditions associated with reduced estrogen production such as menopausal and peri-menopausal symptoms as well as hypoestrogenism. It is also used in transgender hormone therapy, as a component of oral contraceptive pills for preventing pregnancy (most commonly as [DB00977], a synthetic form of estradiol), and is sometimes used for the palliative treatment of some hormone-sensitive cancers like breast and prostate cancer. Estradiol is available in a number of formulations including oral, transdermal, and injectable. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulphate conjugated form, estrone sulphate, are the most abundant circulating estrogens in postmenopausal women [FDA Label]. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems. When used for oral or IM administration, estradiol is commonly synthesized as a pro-drug ester (such as [DB13952], [DB13953], [DB13954], [DB13955], and [DB13956]). It is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter the systemic circulation and exert its estrogenic effects [A12102]. Esterification of estradiol aims to improve absorption after oral administration (such as with Estradiol valerate) or to sustain release from intramuscular depot injections (such as with Estradiol Cypionate) through improved lipophilicity [T84]. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol. Recommendations for treatment of menopausal symptoms changed drastically following the release of results and early termination of the Women's Health Initiative (WHI) studies in 2002 as a number of concerns were raised regarding the use of estrogen [A31626]. Specifically, the combined estrogen–progestin arm was discontinued after approximately five years of follow up due to a statistically significant increase in invasive breast cancer and in cardiovascular events [A31627]. Following extensive critique of the WHI results in the years following its release, Hormone Replacement Therapy (HRT) is now recommended to be used only for a short period (for 3-5 years post-menopause) in low doses, and in women without a history of breast cancer or at increased risk of cardiovascular or thromboembolic disease [A31628]. Notably, use of estrogen for menopausal symptoms should always be accompanied by a progestin component due to estrogen's effects on the endometrium; in women with an intact uterus, unopposed estrogen has been shown to promote the growth of the endometrium which can lead to endometrial hyperplasia and possibly cancer in the long-term. [DB00977] (EE) is a synthetic form of estradiol commonly used as the estrogenic component of most combination Oral Contraceptive Pills (OCPs). Ethinyl Estradiol differs from Estradiol in that it has improved biovailability and greater resistance to metabolism, making it more suitable for oral administration.
DB13954Estradiol cypionateEstradiol Cypionate is a pro-drug ester of [DB00783], a naturally occurring hormone that circulates endogenously within the human body. Estradiol is the most potent form of all mammalian estrogenic steroids and acts as the major female sex hormone. As a pro-drug of estradiol, estradiol cypionate therefore has the same downstream effects within the body through binding to the Estrogen Receptor (ER) including ERα and ERβ subtypes, which are located in various tissues and organs such as the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. [DB00783] is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter systemic circulation and exert its estrogenic effects [A12102]. Esterification of estradiol aims to improve absorption and bioavailability after oral administration (such as with Estradiol Valerate) or to sustain release from depot intramuscular injections (such as with Estradiol Cypionate) through improved lipophilicity. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol. Ester pro-drugs of estradiol are therefore considered to be bioidentical forms of estrogen [T84]. Estradiol cypionate is commercially available as Depo-Estradiol, an intramuscular depot injection used for the treatment of moderate to severe vasomotor symptoms associated with menopause and for the treatment of hypoestrogenism due to hypogonadism [FDA Label]. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women [FDA Label]. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems. Administration of synthetic and bioidentical forms of estrogen, such as estradiol cypionate, has shown to improve these menopausal symptoms.
DB13956Estradiol valerateEstradiol Valerate (also known as E2V) is a pro-drug ester of [DB00783], a naturally occurring hormone that circulates endogenously within the human body. Estradiol is the most potent form of all mammalian estrogenic steroids and acts as the major female sex hormone. As a pro-drug of estradiol, estradiol acetate therefore has the same downstream effects within the body through binding to the Estrogen Receptor (ER) including ERα and ERβ subtypes, which are located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. [DB00783] is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter systemic circulation and exert its estrogenic effects [A12102]. Esterification of estradiol aims to improves absorption and bioavailability after oral administration (such as with Estradiol valerate) or to sustain release from depot intramuscular injections (such as with Estradiol Cypionate) through improved lipophilicity. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol. Ester pro-drugs of estradiol are therefore considered to be bioidentical forms of estrogen [T84]. Estradiol valerate is commercially available as an intramuscular injection as the product Delestrogen and is indicated for the treatment of moderate to severe vasomotor symptoms and vulvovaginal atrophy due to menopause, for the treatment of hypoestrogenism due to hypogonadism, castration or primary ovarian failure, and for the treatment of advanced androgen-dependent carcinoma of the prostate (for palliation only). Estradiol valerate is also available in combination with [DB09123] as the commercially available product Natazia used for the prevention of pregnancy and for the treatment of heavy menstrual bleeding. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulfate conjugated form, estrone sulfate, are the most abundant circulating estrogens in postmenopausal women [FDA Label]. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems. Administration of synthetic and bioidentical forms of estrogen, such as estradiol valerate, has shown to improve these menopausal symptoms.
DB04574Estrone sulfateEstrone sulfate (as estropipate) is a form of estrogen. It has several uses such as: alleviate symptoms of menopause as hormone replacement therapy, treatment some types of infertility, treatment of some conditions leading to underdevelopment of female sexual characteristics, treatment of vaginal atrophy, treatment of some types of breast cancer (particularly in men and postmenopausal women), treatment of prostate cancer and prevention of osteoporosis.
DB00717NorethisteroneNorethisterone (INN, BAN), also known as Norethindrone (USAN), is a synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.
DrugDrug NameTargetType
DB00286Conjugated estrogensEstrogen receptor alphatarget
DB00286Conjugated estrogensCytochrome P450 3A4enzyme
DB00286Conjugated estrogensCytochrome P450 1A2enzyme
DB00286Conjugated estrogensCatechol O-methyltransferaseenzyme
DB00286Conjugated estrogensCanalicular multispecific organic anion transporter 2transporter
DB00286Conjugated estrogensMultidrug resistance-associated protein 4transporter
DB00286Conjugated estrogensMultidrug resistance-associated protein 1transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 1A2transporter
DB00286Conjugated estrogensSodium/bile acid cotransportertransporter
DB00286Conjugated estrogensSolute carrier family 22 member 10transporter
DB00286Conjugated estrogensSolute carrier family 22 member 8transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 1C1transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 1B1transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 2B1transporter
DB00286Conjugated estrogensP-glycoprotein 1transporter
DB00286Conjugated estrogensSolute carrier family 22 member 6transporter
DB00286Conjugated estrogensOrganic solute transporter subunit alphatransporter
DB00286Conjugated estrogensOrganic solute transporter subunit betatransporter
DB00286Conjugated estrogensCanalicular multispecific organic anion transporter 1transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 4A1transporter
DB00286Conjugated estrogensATP-binding cassette sub-family C member 11transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 1B3transporter
DB00286Conjugated estrogensSolute carrier family 22 member 11transporter
DB00286Conjugated estrogensSolute carrier organic anion transporter family member 3A1transporter
DB00286Conjugated estrogensATP-binding cassette sub-family G member 2transporter
DB00286Conjugated estrogensThyroxine-binding globulincarrier
DB00286Conjugated estrogensSex hormone-binding globulincarrier
DB00286Conjugated estrogensSerum albumincarrier
DB00286Conjugated estrogensEstrogen receptor betatarget
DB01395DrospirenoneProgesterone receptortarget
DB01395DrospirenoneMineralocorticoid receptortarget
DB01395DrospirenoneAndrogen receptortarget
DB01395DrospirenoneProstaglandin G/H synthase 2enzyme
DB01395DrospirenoneSerum paraoxonase/arylesterase 1enzyme
DB01395DrospirenoneGlucocorticoid receptortarget
DB01395DrospirenoneCytochrome P450 3A4enzyme
DB00783EstradiolEstrogen receptor alphatarget
DB00783EstradiolNuclear receptor subfamily 1 group I member 2target
DB00783EstradiolSex hormone-binding globulincarrier
DB00783EstradiolEstrogen receptor betatarget
DB00783EstradiolCytochrome P450 1A2enzyme
DB00783EstradiolUDP-glucuronosyltransferase 1-1enzyme
DB00783EstradiolSerum albumincarrier
DB00783EstradiolFatty acid-binding protein, intestinalcarrier
DB00783EstradiolCytochrome P450 3A4enzyme
DB00783EstradiolCytochrome P450 3A5enzyme
DB00783EstradiolCytochrome P450 3A7enzyme
DB00783EstradiolSolute carrier family 22 member 2transporter
DB00783EstradiolSolute carrier family 22 member 1transporter
DB00783EstradiolSolute carrier family 22 member 3transporter
DB00783EstradiolSolute carrier organic anion transporter family member 2B1transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1A2transporter
DB00783EstradiolMultidrug resistance-associated protein 7transporter
DB00783EstradiolSolute carrier family 22 member 11transporter
DB00783EstradiolATP-binding cassette sub-family G member 2transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1B1transporter
DB00783EstradiolP-glycoprotein 1transporter
DB00783EstradiolCytochrome P450 1A1enzyme
DB00783EstradiolCytochrome P450 1B1enzyme
DB00783EstradiolCytochrome P450 2C19enzyme
DB00783EstradiolCytochrome P450 2C8enzyme
DB00783EstradiolCytochrome P450 2C9enzyme
DB00783EstradiolSolute carrier family 22 member 8transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1B3transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1C1transporter
DB00783EstradiolSolute carrier organic anion transporter family member 4A1transporter
DB00783EstradiolNeuronal acetylcholine receptor subunit alpha-4target
DB00783EstradiolNuclear receptor coactivator 2target
DB00783EstradiolG-protein coupled estrogen receptor 1target
DB00783EstradiolATP synthase subunit atarget
DB00783EstradiolBeclin-1target
DB00783EstradiolEstradiol 17-beta-dehydrogenase 2target
DB00783EstradiolEstrogen-related receptor gammatarget
DB13954Estradiol cypionateEstrogen receptor alphatarget
DB13954Estradiol cypionateNuclear receptor subfamily 1 group I member 2target
DB13954Estradiol cypionateSex hormone-binding globulincarrier
DB13954Estradiol cypionateEstrogen receptor betatarget
DB13954Estradiol cypionateCytochrome P450 1A2enzyme
DB13954Estradiol cypionateUDP-glucuronosyltransferase 1-1enzyme
DB13954Estradiol cypionateSerum albumincarrier
DB13954Estradiol cypionateFatty acid-binding protein, intestinalcarrier
DB13954Estradiol cypionateCytochrome P450 3A4enzyme
DB13954Estradiol cypionateCytochrome P450 3A5enzyme
DB13954Estradiol cypionateCytochrome P450 3A7enzyme
DB13954Estradiol cypionateSolute carrier family 22 member 2transporter
DB13954Estradiol cypionateSolute carrier family 22 member 1transporter
DB13954Estradiol cypionateSolute carrier family 22 member 3transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 2B1transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 1A2transporter
DB13954Estradiol cypionateMultidrug resistance-associated protein 7transporter
DB13954Estradiol cypionateSolute carrier family 22 member 11transporter
DB13954Estradiol cypionateATP-binding cassette sub-family G member 2transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 1B1transporter
DB13954Estradiol cypionateP-glycoprotein 1transporter
DB13954Estradiol cypionateCytochrome P450 1A1enzyme
DB13954Estradiol cypionateCytochrome P450 1B1enzyme
DB13954Estradiol cypionateCytochrome P450 2C19enzyme
DB13954Estradiol cypionateCytochrome P450 2C8enzyme
DB13954Estradiol cypionateCytochrome P450 2C9enzyme
DB13954Estradiol cypionateSolute carrier family 22 member 8transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 1B3transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 1C1transporter
DB13954Estradiol cypionateSolute carrier organic anion transporter family member 4A1transporter
DB13954Estradiol cypionateNeuronal acetylcholine receptor subunit alpha-4target
DB13954Estradiol cypionateNuclear receptor coactivator 2target
DB13954Estradiol cypionateG-protein coupled estrogen receptor 1target
DB13954Estradiol cypionateATP synthase subunit atarget
DB13954Estradiol cypionateBeclin-1target
DB13954Estradiol cypionateEstradiol 17-beta-dehydrogenase 2target
DB13954Estradiol cypionateEstrogen-related receptor gammatarget
DB13956Estradiol valerateEstrogen receptor alphatarget
DB13956Estradiol valerateNuclear receptor subfamily 1 group I member 2target
DB13956Estradiol valerateSex hormone-binding globulincarrier
DB13956Estradiol valerateEstrogen receptor betatarget
DB13956Estradiol valerateCytochrome P450 1A2enzyme
DB13956Estradiol valerateUDP-glucuronosyltransferase 1-1enzyme
DB13956Estradiol valerateSerum albumincarrier
DB13956Estradiol valerateFatty acid-binding protein, intestinalcarrier
DB13956Estradiol valerateCytochrome P450 3A4enzyme
DB13956Estradiol valerateCytochrome P450 3A5enzyme
DB13956Estradiol valerateCytochrome P450 3A7enzyme
DB13956Estradiol valerateSolute carrier family 22 member 2transporter
DB13956Estradiol valerateSolute carrier family 22 member 1transporter
DB13956Estradiol valerateSolute carrier family 22 member 3transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 2B1transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 1A2transporter
DB13956Estradiol valerateMultidrug resistance-associated protein 7transporter
DB13956Estradiol valerateSolute carrier family 22 member 11transporter
DB13956Estradiol valerateATP-binding cassette sub-family G member 2transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 1B1transporter
DB13956Estradiol valerateP-glycoprotein 1transporter
DB13956Estradiol valerateCytochrome P450 1A1enzyme
DB13956Estradiol valerateCytochrome P450 1B1enzyme
DB13956Estradiol valerateCytochrome P450 2C19enzyme
DB13956Estradiol valerateCytochrome P450 2C8enzyme
DB13956Estradiol valerateCytochrome P450 2C9enzyme
DB13956Estradiol valerateSolute carrier family 22 member 8transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 1B3transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 1C1transporter
DB13956Estradiol valerateSolute carrier organic anion transporter family member 4A1transporter
DB13956Estradiol valerateNeuronal acetylcholine receptor subunit alpha-4target
DB13956Estradiol valerateNuclear receptor coactivator 2target
DB13956Estradiol valerateG-protein coupled estrogen receptor 1target
DB13956Estradiol valerateATP synthase subunit atarget
DB13956Estradiol valerateBeclin-1target
DB13956Estradiol valerateEstradiol 17-beta-dehydrogenase 2target
DB13956Estradiol valerateEstrogen-related receptor gammatarget
DB04574Estrone sulfateCytochrome P450 1A2enzyme
DB04574Estrone sulfateCytochrome P450 3A4enzyme
DB04574Estrone sulfateEstrogen receptor alphatarget
DB04574Estrone sulfateEstrogen receptor betatarget
DB04574Estrone sulfateSex hormone-binding globulincarrier
DB04574Estrone sulfateSerum albumincarrier
DB04574Estrone sulfateCytochrome P450 2C9enzyme
DB04574Estrone sulfateMultidrug and toxin extrusion protein 1transporter
DB04574Estrone sulfateMultidrug and toxin extrusion protein 2transporter
DB00717NorethisteroneProgesterone receptortarget
DB00717NorethisteroneP-glycoprotein 1transporter
DB00717NorethisteroneCytochrome P450 2C19enzyme
DB00717NorethisteroneSerum albumincarrier
DB00717NorethisteroneSex hormone-binding globulincarrier
DB00717NorethisteroneCYP3Aenzyme
DrugDrug NamePhaseStatusCount
DB00783Estradiol2Recruiting1
DB00396Progesterone2Recruiting1