Vasomotor Symptoms

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.
DB00603Medroxyprogesterone acetateMedroxyprogesterone acetate (INN, USAN, BAN), also known as 17α-hydroxy-6α-methylprogesterone acetate, and commonly abbreviated as MPA, is a steroidal progestin, a synthetic variant of the human hormone progesterone. It is used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis as well as several other indications. MPA is a more potent derivative of its parent compound medroxyprogesterone (MP). While medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, what is normally being administered is MPA and not MP.
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.
DB00715ParoxetineParoxetine is a selective serotonin reuptake inhibitor (SSRI) drug commonly known as Paxil. It has a variety of uses, including the treatment of anxiety disorders, major depression, posttraumatic stress disorder, and symptoms of menopause, among others.[T653] It was approved by the FDA in the early 1990s and marketed by SmithKline Beecham.[L7712,L7715] A unique feature of this drug is that it is highly potent and selective in its inhibition of serotonin reuptake and has little effect on other neurotransmitters.[A31914] Because of its potent inhibition of serotonin reuptake, paroxetine is more likely to cause withdrawal effects upon cessation. Paroxetine is well tolerated in most patients with a similar adverse effect profile to other members of its drug class.[A31914] The controlled release formulation was designed to decrease the likelihood of nausea that is sometimes associated with paroxetine.[L7700,L7742]
DB00285VenlafaxineVenlafaxine (Effexor) is an antidepressant within the serotonin-norepinephrine reuptake inhibitor (SNRI) class of medications. It exerts its effects primarily by blocking the transporters involved in the reuptake of the neurotransmitters serotonin and norepinephrine, therefore leaving more active neurotransmitter in the synapse. Venlafaxine is officially approved for use in the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder, and panic disorder. As of 2014, Canadian clinical practice guidelines recommend venlafaxine as a first-line option for treatment of generalized anxiety, social anxiety, panic disorder, major depressive disorder (MDD), and consider it a second-line option for management of obsessive-compulsive disorder (OCD) [A177226, A177235]. Venlafaxine is also used off-label for prophylaxis of migraine headaches [A177229], for reduction of vasomotor symptoms associated with menopause [A177238], and for management of neuropathic pain (although there is only minimal evidence of efficacy for this condition) [A177232].
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
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
DB00783EstradiolMultidrug resistance protein 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
DB00783EstradiolEstradiol 17-beta-dehydrogenase 2target
DB00783EstradiolEstrogen-related receptor gammatarget
DB00603Medroxyprogesterone acetateProgesterone receptortarget
DB00603Medroxyprogesterone acetateEstrogen receptor alphatarget
DB00603Medroxyprogesterone acetateCytochrome P450 3A4enzyme
DB00603Medroxyprogesterone acetateCytochrome P450 2C8enzyme
DB00603Medroxyprogesterone acetate3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2enzyme
DB00603Medroxyprogesterone acetateCytochrome P450 2C9enzyme
DB00717NorethisteroneProgesterone receptortarget
DB00717NorethisteroneMultidrug resistance protein 1transporter
DB00717NorethisteroneCytochrome P450 2C19enzyme
DB00717NorethisteroneSerum albumincarrier
DB00717NorethisteroneSex hormone-binding globulincarrier
DB00715ParoxetineSodium-dependent serotonin transportertarget
DB00715ParoxetineSodium-dependent noradrenaline transportertarget
DB00715Paroxetine5-hydroxytryptamine receptor 2Atarget
DB00715ParoxetineCytochrome P450 2D6enzyme
DB00715ParoxetineCytochrome P450 2C9enzyme
DB00715ParoxetineMultidrug resistance protein 1transporter
DB00715ParoxetineCytochrome P450 2B6enzyme
DB00715ParoxetineCytochrome P450 1A2enzyme
DB00715ParoxetineCytochrome P450 3A4enzyme
DB00715ParoxetineAlpha-1 adrenergic receptorstarget
DB00715ParoxetineAlpha-2 adrenergic receptorstarget
DB00715ParoxetineBeta adrenergic receptortarget
DB00715ParoxetineDopamine D2 receptortarget
DB00715ParoxetineHistamine H1 receptortarget
DB00715ParoxetineSerotonin Receptorstarget
DB00715ParoxetineMuscarinic acetylcholine receptortarget
DB00715Paroxetine5-hydroxytryptamine receptor 2Btarget
DB00715ParoxetineD(1) dopamine receptortarget
DB00715ParoxetineCytochrome P450 2C19enzyme
DB00285VenlafaxineSodium-dependent serotonin transportertarget
DB00285VenlafaxineSodium-dependent noradrenaline transportertarget
DB00285VenlafaxineCytochrome P450 2D6enzyme
DB00285VenlafaxineCytochrome P450 3A4enzyme
DB00285VenlafaxineSodium-dependent dopamine transportertarget
DB00285VenlafaxineMultidrug resistance protein 1transporter
DB00285VenlafaxineATP-binding cassette sub-family G member 2transporter
DrugDrug NamePhaseStatusCount
DB00603Medroxyprogesterone acetate2Completed1
DB09153Sodium chloride2Recruiting2
DB05052MF1013Unknown Status1
DB01175EscitalopramNot AvailableCompleted1
DB00996GabapentinNot AvailableWithdrawn1