Premature Ovarian Failure (POF)

Also known as: Primary ovarian failure / Premature Ovarian Failure / Ovarian failure / Primary Ovarian Insufficiency / Ovarian failure primary

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]
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.
DB09381Estrogens, esterifiedEsterified estrogens contain a mixture of estrogenic substances; the principle component is estrone. Preparations contain 75% to 85% sodium estrone sulfate and 6% to 15% sodium equilin sulfate such that the total is not <90%. Esterified estrogens are a man-made mixture of estrogens that are used to treat symptoms of menopause such as hot flashes, vaginal dryness, vaginal burning or irritation, or other hormonal changes in the vagina. It is being also for the prevention and treatment of osteoporosis.
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.
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 estrogensMultidrug resistance protein 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
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 valerateMultidrug resistance protein 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
DB09381Estrogens, esterifiedCytochrome P450 3A4enzyme
DB09381Estrogens, esterifiedThyroxine-binding globulincarrier
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
DrugDrug NamePhaseStatusCount
DB01708Prasterone0Withdrawn1
DB00007Leuprolide2Completed1
DB00097Choriogonadotropin alfa4Completed1
DB09126Chorionic Gonadotropin (Human)4Completed1
DB00783Estradiol4Completed2
DB00977Ethinylestradiol4Completed1
DB00099Filgrastim4Active Not Recruiting1
DB00066Follitropin4Completed1
DB06785Ganirelix4Completed2
DB00717Norethisterone4Completed1
DB00396Progesterone4Completed1
DB09153Sodium chloride4Active Not Recruiting1
DB06825Triptorelin4Completed1
DB00066FollitropinNot AvailableUnknown Status1
DB00094UrofollitropinNot AvailableCompleted1