Drospirenone is a

progestin A progestogen, also referred to as 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. ...

and antiandrogen medication which is used in birth control pills to prevent

pregnancy Pregnancy is the time during which one or more offspring gestation, gestates inside a woman's uterus. A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Conception (biology), Conception usually occurs ...

and in

menopausal hormone therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

, among other uses. It is available both alone under the brand name Slynd and in combination with an

estrogen Estrogen (also spelled oestrogen in British English; see spelling differences) is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three ...

under the brand name Yasmin among others. The medication is an analog of the drug spironolactone. Drospirenone is taken

by mouth Oral administration is a route of administration whereby a substance is taken through the Human mouth, mouth, swallowed, and then processed via the digestive system. This is a common route of administration for many medications. Oral administ ...

. Common

side effect In medicine, a side effect is an effect of the use of a medicinal drug or other treatment, usually adverse but sometimes beneficial, that is unintended. Herbal and traditional medicines also have side effects. A drug or procedure usually use ...

s include

acne Acne ( ), also known as ''acne vulgaris'', is a long-term Cutaneous condition, skin condition that occurs when Keratinocyte, dead skin cells and Sebum, oil from the skin clog hair follicles. Typical features of the condition include comedo, ...

headache A headache, also known as cephalalgia, is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of Depression (mood), depression in those with severe ...

, breast tenderness, weight increase, and menstrual changes. Rare side effects may include high potassium levels and blood clots (when taken as a combined oestrogen-progestogen pill), among others. Drospirenone is a progestin, or a synthetic progestogen, and hence is an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

of the progesterone receptor, the

biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

of progestogens like

progesterone Progesterone (; P4) is an endogenous steroid and progestogen sex hormone involved in the menstrual cycle, pregnancy, and embryogenesis of humans and other species. It belongs to a group of steroid hormones called the progestogens and is the ma ...

. It has additional antimineralocorticoid and antiandrogenic activity and no other important

hormonal A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs or tissues by complex biological processes to regulate physiology and behavior. Hormones a ...

activity. Because of its antimineralocorticoid activity and lack of undesirable

off-target activity Off-target activity is biological activity of a drug that is different from and not at that of its intended biological target. It most commonly contributes to side effects. However, in some cases, off-target activity can be taken advantage of for t ...

, drospirenone is said to more closely resemble bioidentical

than other progestins. Drospirenone was patented in 1976 and introduced for medical use in 2000. It is available widely throughout the world. The medication is sometimes referred to as a "fourth-generation" progestin. It is available as a

generic medication A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...

.Generic Yasmin Availability
via at Drugs.com In 2020, a formulation of drospirenone with ethinylestradiol was the 145th most commonly prescribed medication in the United States, with more than 4million prescriptions.

Medical uses

Drospirenone (DRSP) is used by itself as a progestogen-only birth control pill, in combination with the estrogens ethinylestradiol (EE) or estetrol (E4), with or without supplemental

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

( vitamin B₉), as a combined birth control pill, and in combination with the estrogen estradiol (E2) for use in

. A birth control pill with low-dose ethinylestradiol is also indicated for the treatment of moderate

premenstrual syndrome Premenstrual syndrome (PMS) is a disruptive set of emotional and physical symptoms that regularly occur in the one to two weeks before the start of each menstrual period. Symptoms resolve around the time menstrual bleeding begins. Symptoms v ...

(PMS), premenstrual dysphoric disorder (PMDD), and

dysmenorrhea Dysmenorrhea, also known as period pain, painful periods or menstrual cramps, is pain during menstruation. Its usual onset occurs around the time that menstruation begins. Symptoms typically last less than three days. The pain is usually in th ...

(painful menstruation). For use in menopausal hormone therapy, E2/DRSP is specifically approved to treat moderate to severe vasomotor symptoms (hot flashes), vaginal atrophy, and postmenopausal osteoporosis. The drospirenone component in this formulation is included specifically to prevent estrogen-induced endometrial hyperplasia. Drospirenone has also been used in combination with an estrogen as a component of hormone therapy for transgender women. Studies have found that EE/DRSP is superior to

placebo A placebo ( ) can be roughly defined as a sham medical treatment. Common placebos include inert tablets (like sugar pills), inert injections (like saline), sham surgery, and other procedures. Placebos are used in randomized clinical trials ...

in reducing premenstrual emotional and physical symptoms while also improving

quality of life Quality of life (QOL) is defined by the World Health Organization as "an individual's perception of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards ...

. E2/DRSP has been found to increase bone mineral density and to reduce the occurrence of

bone fracture A bone fracture (abbreviated FRX or Fx, Fx, or #) is a medical condition in which there is a partial or complete break in the continuity of any bone in the body. In more severe cases, the bone may be broken into several fragments, known as a ''c ...

s in

postmenopausal Menopause, also known as the climacteric, is the time when menstrual periods permanently stop, marking the end of the reproductive stage for the female human. It typically occurs between the ages of 45 and 55, although the exact timing can ...

women. In addition, E2/DRSP has a favorable influence on

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

and

triglyceride A triglyceride (from '' tri-'' and '' glyceride''; also TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids. Triglycerides are the main constituents of body fat in humans and other vertebrates ...

levels and decreases

blood pressure Blood pressure (BP) is the pressure of Circulatory system, circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term ...

in women with

high blood pressure Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...

. Due to its antimineralocorticoid activity, drospirenone opposes estrogen-induced

salt In common usage, salt is a mineral composed primarily of sodium chloride (NaCl). When used in food, especially in granulated form, it is more formally called table salt. In the form of a natural crystalline mineral, salt is also known as r ...

and water retention and maintains or slightly reduces body weight.

Available forms

Drospirenone is available in the following formulations, brand names, and indications: * Drospirenone 4 mg (''Slynd'') – progestogen-only birth control pill * Drospirenone 3 mg and estetrol 14.2 mg (''Nextstellis'' (US)) – combined birth control pill * Ethinylestradiol 30 μg and drospirenone 3 mg (''Ocella'', ''Syeda'', ''Yasmin'', ''Zarah'', ''Zumandimine'') – combined birth control pill * Ethinylestradiol 20 μg and drospirenone 3 mg (''Gianvi'', ''Jasmiel'', ''Loryna'', ''Lo-Zumandimine'', ''Nikki'', ''Vestura'', ''Yaz'') – combined birth control pill, acne, PMS, PMDD, dysmenorrhea * Ethinylestradiol 30 μg, drospirenone 3 mg, and levomefolate calcium 0.451 mg (''Beyaz'', ''Tydemy'') – combined birth control pill with vitamin B₉ supplementation, acne, PMS * Estetrol 15 mg and drospirenone 3 mg (''Nextstellis'' (CA)) – combined birth control pill * Estradiol 0.5 or 1 mg and drospirenone 0.25 or 0.5 mg (''Angeliq'') – menopausal hormone therapy (menopausal syndrome, postmenopausal osteoporosis)

Contraindications

Contraindications of drospirenone include renal impairment or

chronic kidney disease Chronic kidney disease (CKD) is a type of long-term kidney disease, defined by the sustained presence of abnormal kidney function and/or abnormal kidney structure. To meet criteria for CKD, the abnormalities must be present for at least three mo ...

, adrenal insufficiency, presence or history of cervical cancer or other progestogen-sensitive cancers, benign or malignant liver tumors or hepatic impairment, undiagnosed abnormal uterine bleeding, and hyperkalemia (high potassium levels). Renal impairment, hepatic impairment, and adrenal insufficiency are contraindicated because they increase exposure to drospirenone and/or increase the risk of hyperkalemia with drospirenone.

Side effects

Adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s of drospirenone alone occurring in more than 1% of women may include unscheduled menstrual bleeding ( breakthrough or intracyclic) (40.3–64.4%),

(3.8%), metrorrhagia (2.8%),

(2.7%), breast pain (2.2%), weight gain (1.9%),

(1.9%),

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. It can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the throat. Over 30 d ...

(1.8%), vaginal hemorrhage (1.7%), decreased libido (1.3%), breast tenderness (1.2%), and irregular menstruation (1.2%).

High potassium levels

Drospirenone is an antimineralocorticoid with

potassium Potassium is a chemical element; it has Symbol (chemistry), symbol K (from Neo-Latin ) and atomic number19. It is a silvery white metal that is soft enough to easily cut with a knife. Potassium metal reacts rapidly with atmospheric oxygen to ...

-sparing properties, though in most cases no increase of potassium levels is to be expected. In women with mild or moderate chronic kidney disease, or in combination with chronic daily use of other potassium-sparing medications (

ACE inhibitor Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. This class of medicine works by causing relaxation of blood vessels as well as a decr ...

angiotensin II receptor antagonist Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...

s, potassium-sparing diuretics,

heparin Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Heparin is a blood anticoagulant that increases the activity of antithrombin. It is used in the treatment of myocardial infarction, ...

, antimineralocorticoids, or

nonsteroidal anti-inflammatory drug Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents bl ...

s), a potassium level should be checked after two weeks of use to test for hyperkalemia. Persistent hyperkalemia that required discontinuation occurred in 2 out of around 1,000 women (0.2%) with 4 mg/day drospirenone alone in clinical trials.

Blood clots

Birth control pills containing ethinylestradiol and a progestin are associated with an increased risk of venous thromboembolism (VTE), including

deep vein thrombosis Deep vein thrombosis (DVT) is a type of venous thrombosis involving the formation of a blood clot in a deep vein, most commonly in the legs or pelvis. A minority of DVTs occur in the arms. Symptoms can include pain, swelling, redness, and enl ...

(DVT) and

pulmonary embolism Pulmonary embolism (PE) is a blockage of an pulmonary artery, artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include dyspnea, shortness of breath, chest pain ...

(PE). The incidence is about 4-fold higher on average than in women not taking a birth control pill. The absolute risk of VTE with ethinylestradiol-containing birth control pills is small, in the area of 3 to 10 out of 10,000 women per year, relative to 1 to 5 out of 10,000 women per year not taking a birth control pill. The risk of VTE during

is 5 to 20 in 10,000 women per year and during the

postpartum period The postpartum (or postnatal) period begins after childbirth and is typically considered to last for six to eight weeks. There are three distinct phases of the postnatal period; the acute phase, lasting for six to twelve hours after birth; the ...

is 40 to 65 per 10,000 women per year. The higher risk of VTE with combined birth control pills is thought to be due to the ethinylestradiol component, as ethinylestradiol has estrogenic effects on liver synthesis of coagulation factors which result in a procoagulatory state. In contrast to ethinylestradiol-containing birth control pills, neither progestogen-only birth control nor the combination of

transdermal Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointm ...

estradiol and an oral progestin in

is associated with an increased risk of VTE. Different progestins in ethinylestradiol-containing birth control pills have been associated with different risks of VTE. Birth control pills containing progestins such as desogestrel, gestodene, drospirenone, and

cyproterone acetate Cyproterone acetate (CPA), sold alone under the brand name Androcur or Ethinylestradiol/cyproterone acetate, with ethinylestradiol under the brand names Diane or Diane-35 among others, is an antiandrogen and progestin medication used in the tre ...

have been found to have 2- to 3-fold the risk of VTE of birth control pills containing levonorgestrel in retrospective cohort and nested case–control

observational studies In fields such as epidemiology, social sciences, psychology and statistics, an observational study draws inferences from a sample to a population where the independent variable is not under the control of the researcher because of ethical conc ...

. However, this area of research is controversial, and

confounding factor In causal inference, a confounder is a variable that influences both the dependent variable and independent variable, causing a spurious association. Confounding is a causal concept, and as such, cannot be described in terms of correlati ...

s may have been present in these studies. Other observational studies, specifically prospective cohort and case control studies, have found no differences in risk between different progestins, including between birth control pills containing drospirenone and birth control pills containing levonorgestrel. These kinds of observational studies have certain advantages over the aforementioned types of studies, like better ability to control for confounding factors.

Systematic review A systematic review is a scholarly synthesis of the evidence on a clearly presented topic using critical methods to identify, define and assess research on the topic. A systematic review extracts and interprets data from published studies on ...

s and

meta-analyses Meta-analysis is a method of synthesis of quantitative data from multiple independent studies addressing a common research question. An important part of this method involves computing a combined effect size across all of the studies. As such, th ...

of all of the data in the mid-to-late 2010s found that birth control pills containing cyproterone acetate, desogestrel, drospirenone, or gestodene overall were associated with a risk of VTE of about 1.3- to 2.0-fold compared to that of levonorgestrel-containing birth control pills.

Androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

ic progestins have been found to antagonize to some degree the effects of ethinylestradiol on coagulation. As a result, more androgenic progestins, like levonorgestrel and

norethisterone Norethisterone, also known as norethindrone and sold under the brand name Norlutin among others, is a progestin medication used in birth control pills, menopausal hormone therapy, and for the treatment of gynecological disorders. The medicatio ...

, may oppose the procoagulatory effects of ethinylestradiol and result in a lower increase in risk of VTE. Conversely, this would be the case less or not at all with progestins that are less androgenic, like desogestrel and gestodene, as well as with progestins that are antiandrogenic, like drospirenone and cyproterone acetate. In the early 2010s, the FDA updated the label for birth control pills containing drospirenone and other progestins to include warnings for stopping use prior to and after surgery, and to warn that such birth control pills may have a higher risk of blood clots.

Breast cancer

Drospirenone has been found to stimulate the proliferation and

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

breast cancer Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a Breast lump, lump in the breast, a change in breast shape, dimpling of the skin, Milk-rejection sign, milk rejection, fluid coming from the nipp ...

cells in preclinical research, similarly to certain other progestins. However, some evidence suggests that drospirenone may do this more weakly than certain other progestins, like medroxyprogesterone acetate. The combination of estradiol and drospirenone has been found to increase breast density, an established risk factor for breast cancer, in postmenopausal women. Data on risk of

in women with newer progestins like drospirenone are lacking at present. Progestogen-only birth control is not generally associated with a higher risk of breast cancer. Conversely, combined birth control and menopausal hormone therapy with an estrogen and a progestogen are associated with higher risks of breast cancer.

Overdose

These have been no reports of serious

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. The term compli ...

s with

overdose A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended. Retrieved on September 20, 2014.

of drospirenone. Symptoms that may occur in the event of an overdose may include

vomiting Vomiting (also known as emesis, puking and throwing up) is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteritis, pre ...

, and vaginal bleeding. There is no antidote for overdose of drospirenone and treatment of overdose should be based on

symptom Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

s. Since drospirenone has antimineralocorticoid activity, levels of

and

sodium Sodium is a chemical element; it has Symbol (chemistry), symbol Na (from Neo-Latin ) and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 element, group 1 of the peri ...

should be measured and signs of metabolic acidosis should be monitored.

Interactions

Inhibitors and inducers of the

cytochrome P450 Cytochromes P450 (P450s or CYPs) are a Protein superfamily, superfamily of enzymes containing heme as a cofactor (biochemistry), cofactor that mostly, but not exclusively, function as monooxygenases. However, they are not omnipresent; for examp ...

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

CYP3A4 Cytochrome P450 3A4 (abbreviated CYP3A4) () is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by ''CYP3A4'' gene. It organic redox reaction, oxidizes small foreign organic molecules ( ...

may influence the levels and efficacy of drospirenone. Treatment for 10 days with 200 mg twice daily

ketoconazole Ketoconazole, sold under the brand name Nizoral, among others, is an antiandrogen, antifungal drug, antifungal, and antiglucocorticoid medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin inf ...

, a strong CYP3A4 inhibitor among other actions, has been found to result in a moderate 2.0- to 2.7-fold increase in exposure to drospirenone. Drospirenone does not appear to influence the

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

of omeprazole (metabolized via CYP2C19),

simvastatin Simvastatin, sold under the brand name Zocor among others, is a statin, a type of lipid-lowering medication. It is used along with exercise, diet, and weight loss to decrease hyperlipidemia, elevated lipid levels. It is also used to decrease t ...

(metabolized via CYP3A4), or

midazolam Midazolam, sold under the brand name Versed among others, is a benzodiazepine medication used for anesthesia, premedication before surgical anesthesia, and procedural sedation, and to treat psychomotor agitation, severe agitation. It induces ...

(metabolized via CYP3A4), and likely does not influence the metabolism of other medications that are metabolized via these pathways. Drospirenone may interact with

-sparing medications such as

s, potassium-sparing diuretics, potassium supplements,

, antimineralocorticoids, and

s to further increase potassium levels. This may increase the risk of hyperkalemia (high potassium levels).

Pharmacology

Pharmacodynamics

Drospirenone binds with high

affinity Affinity may refer to: Commerce, finance and law * Affinity (law), kinship by marriage * Affinity analysis, a market research and business management technique * Affinity Credit Union, a Saskatchewan-based credit union * Affinity Equity Pa ...

to the progesterone receptor (PR) and

mineralocorticoid receptor The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the ''NR3C2'' gene that is located on chromosome 4q31 ...

(MR), with lower affinity to the

androgen receptor The androgen receptor (AR), also known as NR3C4 (nuclear receptor subfamily 3, group C, member 4), is a type of nuclear receptor that is activated by binding any of the androgenic hormones, including testosterone and dihydrotestosterone, in th ...

(AR), and with very low affinity to the

glucocorticoid receptor The glucocorticoid receptor (GR or GCR) also known by its gene name ''NR3C1'' ( nuclear receptor subfamily 3, group C, member 1) is the steroid receptor for glucocorticoids such as cortisol. The GR is expressed in almost every cell in the bod ...

(GR). It is an

of the PR and an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.progestogen, antimineralocorticoid, and antiandrogen. Drospirenone has no

ic activity and no appreciable

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

or antiglucocorticoid activity.

Progestogenic activity

Drospirenone is an

of the PR, the

of progestogens like

. It has about 35% of the affinity of promegestone for the PR and about 19 to 70% of the affinity of progesterone for the PR. Drospirenone has antigonadotropic and functional antiestrogenic effects as a result of PR activation. The

ovulation Ovulation is an important part of the menstrual cycle in female vertebrates where the egg cells are released from the ovaries as part of the ovarian cycle. In female humans ovulation typically occurs near the midpoint in the menstrual cycle and ...

-inhibiting dosage of drospirenone is 2 to 3 mg/day. Inhibition of ovulation occurred in about 90% of women at a dose of 0.5 to 2 mg/day and in 100% of women at a dose of 3 mg/day. The total endometrial transformation dose of drospirenone is about 50 mg per cycle, whereas its daily dose is 2 mg for partial transformation and 4 to 6 mg for full transformation. The medication acts as a contraceptive by activating the PR, which suppresses the

secretion Secretion is the movement of material from one point to another, such as a secreted chemical substance from a cell or gland. In contrast, excretion is the removal of certain substances or waste products from a cell or organism. The classical mec ...

of luteinizing hormone, inhibits ovulation, and alters the cervical membrane and

endometrium The endometrium is the inner epithelium, epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer: the basal layer contains stem cells which regenerate the functional layer. The funct ...

. Due to its antigonadotropic effects, drospirenone inhibits the secretion of the gonadotropins, luteinizing hormone (LH) and

follicle-stimulating hormone Follicle-stimulating hormone (FSH) is a gonadotropin, a glycoprotein polypeptide hormone. FSH is synthesized and secreted by the gonadotropic cells of the anterior pituitary gland and regulates the development, growth, puberty, pubertal maturat ...

(FSH), and suppresses

gonad A gonad, sex gland, or reproductive gland is a Heterocrine gland, mixed gland and sex organ that produces the gametes and sex hormones of an organism. Female reproductive cells are egg cells, and male reproductive cells are sperm. The male gon ...

al sex hormone production, including of estradiol,

, and

testosterone Testosterone is the primary male sex hormone and androgen in Male, males. In humans, testosterone plays a key role in the development of Male reproductive system, male reproductive tissues such as testicles and prostate, as well as promoting se ...

. Drospirenone alone at 4 mg/day has been found to suppress estradiol levels in premenopausal women to about 40 to 80 pg/mL depending on the time of the cycle. No studies of the antigonadotropic effects of drospirenone or its influence on hormone levels appear to have been conducted in men. In male

cynomolgus monkey The crab-eating macaque (''Macaca fascicularis''), also known as the long-tailed macaque or cynomolgus macaque, is a cercopithecine primate native to Southeast Asia. As a synanthropic species, the crab-eating macaque thrives near human settlem ...

s however, 4 mg/kg/day oral drospirenone strongly suppressed

levels.

Antimineralocorticoid activity

Drospirenone is an

antagonist An antagonist is a character in a story who is presented as the main enemy or rival of the protagonist and is often depicted as a villain.biological target A biological target is anything within a living organism to which some other entity (like an endogenous ligand or a drug) is directed and/or binds, resulting in a change in its behavior or function. Examples of common classes of biological targets ...

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

s like

aldosterone Aldosterone is the main mineralocorticoid steroid hormone produced by the zona glomerulosa of the adrenal cortex in the adrenal gland. It is essential for sodium conservation in the kidney, salivary glands, sweat glands, and colon. It plays ...

, and hence is an antimineralocorticoid. It has about 100 to 500% of the affinity of aldosterone for the MR and about 50 to 230% of the affinity of progesterone for the MR. Drospirenone is about 5.5 to 11 times more potent as an antimineralocorticoid than spironolactone in animals. Accordingly, 3 to 4 mg drospirenone is said to be equivalent to about 20 to 25 mg spironolactone in terms of antimineralocorticoid activity. It has been said that the

pharmacological Pharmacology is the science of drugs and medications, including a substance's origin, composition, pharmacokinetics, pharmacodynamics, therapeutic use, and toxicology. More specifically, it is the study of the interactions that occur between ...

profile of drospirenone more closely resembles that of progesterone than other progestins due to its antimineralocorticoid activity. Drospirenone is the only clinically used progestogen with prominent antimineralocorticoid activity besides progesterone. For comparison to progesterone, a 200 mg dose of oral progesterone is considered to be approximately equivalent in antimineralocorticoid effect to a 25 to 50 mg dose of spironolactone. Both drospirenone and progesterone are actually weak

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

s of the MR in the absence of

s. Due to its antimineralocorticoid activity, drospirenone increases

natriuresis Natriuresis is the process of sodium excretion in the urine through the action of the kidneys. It is promoted by Brain natriuretic peptide, ventricular and atrial natriuretic peptides as well as calcitonin, and inhibited by chemicals such as aldost ...

, decreases water retention and

, and produces compensatory increases in plasma renin activity as well as circulating levels and urinary

excretion Excretion is elimination of metabolic waste, which is an essential process in all organisms. In vertebrates, this is primarily carried out by the lungs, Kidney (vertebrates), kidneys, and skin. This is in contrast with secretion, where the substa ...

. This has been shown to occur at doses of 2 to 4 mg/day. Similar effects occur during the

luteal phase The menstrual cycle is on average 28 days in length. It begins with Menstruation, menses (day 1–7) during the follicular phase (day 1–14), followed by ovulation (day 14) and ending with the luteal phase (day 14–28). While historically, medi ...

of the

menstrual cycle The menstrual cycle is a series of natural changes in hormone production and the structures of the uterus and ovaries of the female reproductive system that makes pregnancy possible. The ovarian cycle controls the production and release of eg ...

due to increased progesterone levels and the resulting antagonism of the MR. Estrogens, particularly ethinylestradiol, activate liver production of angiotensinogen and increase levels of angiotensinogen and

angiotensin II Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the ...

, thereby activating the renin–angiotensin–aldosterone system. As a result, they can produce undesirable side effects including increased

excretion, water retention, weight gain, and increased blood pressure. Progesterone and drospirenone counteract these undesirable effects via their antimineralocorticoid activity. Accumulating research indicates that antimineralocorticoids like drospirenone and spironolactone may also have positive effects on

adipose tissue Adipose tissue (also known as body fat or simply fat) is a loose connective tissue composed mostly of adipocytes. It also contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, Blood vessel, vascular endothel ...

and

metabolic Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the ...

health.

Antiandrogenic activity

Drospirenone is an antagonist of the AR, the biological target of

androgen An androgen (from Greek ''andr-'', the stem of the word meaning ) is any natural or synthetic steroid hormone that regulates the development and maintenance of male characteristics in vertebrates by binding to androgen receptors. This includes ...

s like

and dihydrotestosterone (DHT). It has about 1 to 65% of the affinity of the synthetic

anabolic steroid Anabolic steroids, also known as anabolic-androgenic steroids (AAS), are a class of drugs that are structurally related to testosterone, the main male sex hormone, and produce effects by binding to the androgen receptor (AR). Anabolism, Anaboli ...

metribolone for the AR. The medication is more potent as an antiandrogen than spironolactone, but is less potent than

, with about 30% of its antiandrogenic activity in animals. Progesterone displays antiandrogenic activity in some assays similarly to drospirenone, although this issue is controversial and many researchers regard progesterone as having no significant antiandrogenic activity. Drospirenone shows antiandrogenic effects on the serum

lipid profile A lipid profile or lipid panel is a Test panel, panel of blood tests used to find abnormalities in blood lipid ( such as cholesterol and triglycerides) concentrations. The results of this test can identify certain Inborn error of lipid metabolis ...

, including higher HDL

and

levels and lower LDL cholesterol levels, at a dose of 3 mg/day in women. The medication does not inhibit the effects of ethinylestradiol on sex hormone-binding globulin (SHBG) and serum lipids, in contrast to androgenic progestins like levonorgestrel but similarly to other antiandrogenic progestins like cyproterone acetate. SHBG levels are significantly higher with ethinylestradiol and cyproterone acetate than with ethinylestradiol and drospirenone, owing to the more potent antiandrogenic activity of cyproterone acetate relative to drospirenone.

ic progestins like levonorgestrel have been found to inhibit the procoagulatory effects of estrogens like ethinylestradiol on hepatic synthesis of coagulation factors, whereas this may occur less or not at all with weakly androgenic progestins like desogestrel and antiandrogenic progestins like drospirenone.

Other activity

Drospirenone stimulates the proliferation of MCF-7

cells ''

in vitro ''In vitro'' (meaning ''in glass'', or ''in the glass'') Research, studies are performed with Cell (biology), cells or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in ...

'', an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1). Certain other progestins act similarly in this assay, whereas

acts neutrally. It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in

clinical studies Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...

Pharmacokinetics

Absorption

The

oral The word oral may refer to: Relating to the mouth * Relating to the mouth, the first portion of the alimentary canal that primarily receives food and liquid **Oral administration of medicines ** Oral examination (also known as an oral exam or ora ...

bioavailability of drospirenone is between 66 and 85%. Peak levels occur 1 to 6 hours after an oral dose. Levels are about 27 ng/mL after a single 4 mg dose. There is 1.5- to 2-fold accumulation in drospirenone levels with continuous administration, with steady-state levels of drospirenone achieved after 7 to 10 days of administration. Peak levels of drospirenone at steady state with 4 mg/day drospirenone are about 41 ng/mL. With the combination of 30 μg/day ethinylestradiol and 3 mg/day drospirenone, peak levels of drospirenone after a single dose are 35 ng/mL, and levels at steady state are 60 to 87 ng/mL at peak and 20 to 25 ng/mL at trough. The

pharmacokinetics Pharmacokinetics (from Ancient Greek ''pharmakon'' "drug" and ''kinetikos'' "moving, putting in motion"; see chemical kinetics), sometimes abbreviated as PK, is a branch of pharmacology dedicated to describing how the body affects a specific su ...

of oral drospirenone are linear with a single dose across a dose range of 1 to 10 mg. Intake of drospirenone with

food Food is any substance consumed by an organism for Nutrient, nutritional support. Food is usually of plant, animal, or Fungus, fungal origin and contains essential nutrients such as carbohydrates, fats, protein (nutrient), proteins, vitamins, ...

does not influence the absorption of drospirenone.

Distribution

The distribution half-life of drospirenone is about 1.6 to 2 hours. The apparent volume of distribution of drospirenone is approximately 4 L/kg. The plasma protein binding of drospirenone is 95 to 97%. It is bound to

albumin Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water- soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Alb ...

and 3 to 5% circulates freely or unbound. Drospirenone has no

for sex hormone-binding globulin (SHBG) or corticosteroid-binding globulin (CBG), and hence is not bound by these plasma proteins in the circulation.

Metabolism

The

of drospirenone is extensive. It is metabolized into the

acid An acid is a molecule or ion capable of either donating a proton (i.e. Hydron, hydrogen cation, H+), known as a Brønsted–Lowry acid–base theory, Brønsted–Lowry acid, or forming a covalent bond with an electron pair, known as a Lewis ...

form of drospirenone by opening of its lactone ring. The medication is also metabolized by reduction of its

double bond In chemistry, a double bond is a covalent bond between two atoms involving four bonding electrons as opposed to two in a single bond. Double bonds occur most commonly between two carbon atoms, for example in alkenes. Many double bonds exist betw ...

between the C4 and C5 positions and subsequent sulfation. The two major

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...

s of drospirenone are drospirenone acid and 4,5-dihydrodrospirenone 3-sulfate, and are both formed independently of the

system. Neither of these metabolites are known to be pharmacologically active. Drospirenone also undergoes oxidative metabolism by

Elimination

Drospirenone is excreted in

urine Urine is a liquid by-product of metabolism in humans and many other animals. In placental mammals, urine flows from the Kidney (vertebrates), kidneys through the ureters to the urinary bladder and exits the urethra through the penile meatus (mal ...

and

feces Feces (also known as faeces American and British English spelling differences#ae and oe, or fæces; : faex) are the solid or semi-solid remains of food that was not digested in the small intestine, and has been broken down by bacteria in the ...

, with slightly more excreted in feces than in urine. Only trace amounts of unchanged drospirenone can be found in urine and feces. At least 20 different

s can be identified in urine and feces. Drospirenone and its metabolites are excreted in urine about 38% as glucuronide conjugates, 47% as sulfate conjugates, and less than 10% in unconjugated form. In feces, excretion is about 17% glucuronide conjugates, 20% sulfate conjugates, and 33% unconjugated. The

elimination half-life Biological half-life (elimination half-life, pharmacological half-life) is the time taken for concentration of a biological substance (such as a medication) to decrease from its maximum concentration ( Cmax) to half of Cmax in the blood plasma. ...

of drospirenone is between 25 and 33 hours. The half-life of drospirenone is unchanged with repeated administration. Elimination of drospirenone is virtually complete 10 days after the last dose.

Chemistry

Drospirenone, also known as 1,2-dihydrospirorenone or as 17β-hydroxy-6β,7β:15β,16β-dimethylene-3-oxo-17α-pregn-4-ene-21-carboxylic acid, γ-lactone, is a synthetic

steroid A steroid is an organic compound with four fused compound, fused rings (designated A, B, C, and D) arranged in a specific molecular configuration. Steroids have two principal biological functions: as important components of cell membranes t ...

al 17α-spirolactone, or more simply a spirolactone. It is an analogue of other spirolactones like spironolactone, canrenone, and spirorenone. Drospirenone differs structurally from spironolactone only in that the C7α

acetyl In organic chemistry, an acetyl group is a functional group denoted by the chemical formula and the structure . It is sometimes represented by the symbol Ac (not to be confused with the element actinium). In IUPAC nomenclature, an acetyl grou ...

thio substitution of spironolactone has been removed and two methylene groups have been substituted in at the C6β–7β and C15β–16β positions. Spirolactones like drospirenone and spironolactone are

derivative In mathematics, the derivative is a fundamental tool that quantifies the sensitivity to change of a function's output with respect to its input. The derivative of a function of a single variable at a chosen input value, when it exists, is t ...

s of

, which likewise has progestogenic and antimineralocorticoid activity. The loss of the C7α acetylthio group of spironolactone, a compound with negligible progestogenic activity, appears to be involved in the restoration of progestogenic activity in drospirenone, as SC-5233, the analogue of spironolactone without a C7α substitution, has potent progestogenic activity similarly to drospirenone.

History

Drospirenone was patented in 1976 and introduced for medical use in 2000. Schering AG of

Germany Germany, officially the Federal Republic of Germany, is a country in Central Europe. It lies between the Baltic Sea and the North Sea to the north and the Alps to the south. Its sixteen States of Germany, constituent states have a total popu ...

has been granted several patents on the production of drospirenone, including WIPO and US patents, granted in 1998 and 2000, respectively. It was introduced for medical use in combination with ethinylestradiol as a combined birth control pill in 2000. Drospirenone is sometimes described as a "fourth-generation" progestin based on its time of introduction. The medication was approved for use in

in combination with estradiol in 2005. Drospirenone was introduced for use as a progestogen-only birth control pill in 2019. A combined birth control pill containing estetrol and drospirenone was approved in 2021.

Society and culture

Generic names

''Drospirenone'' is the generic name of the drug and its , , , and , while ''drospirénone'' is its .drospirenone at Drugs.com: Its name is a shortened form of the name ''1,2-dihydrospirorenone'' or ''dihydrospirenone''. Drospirenone is also known by its developmental code names ''SH-470'' and ''ZK-30595'' (alone), ''BAY 86-5300'', ''BAY 98-7071'', and ''SH-T-00186D'' (in combination with ethinylestradiol), ''BAY 86-4891'' (in combination with estradiol), and ''FSN-013'' (in combination with estetrol).

Brand names

Drospirenone is marketed in combination with an estrogen under a variety of brand names throughout the world. Among others, it is marketed in combination with ethinylestradiol under the brand names Yasmin and Yaz, in combination with estetrol under the brand name Nextstellis, and in combination with estradiol under the brand name Angeliq.

Availability

Drospirenone is marketed widely throughout the world.

Generation

Drospirenone has been categorized as a "fourth-generation" progestin.

Litigation

Many lawsuits have been filed against

Bayer Bayer AG (English: , commonly pronounced ; ) is a German multinational pharmaceutical and biotechnology company and is one of the largest pharmaceutical companies and biomedical companies in the world. Headquartered in Leverkusen, Bayer' ...

, the manufacturer of drospirenone, due to the higher risk of venous thromboembolism (VTE) that has been observed with combined birth control pills containing drospirenone and certain other progestins relative to the risk with levonorgestrel-containing combined birth control pills. In July 2012, Bayer notified its stockholders that there were more than 12,000 such lawsuits against the company involving Yaz, Yasmin, and other birth control pills with drospirenone. They also noted that the company by then had settled 1,977 cases for US$402.6 million, for an average of US$212,000 per case, while setting aside US$610.5 million to settle the others. As of 17 July 2015, there have been at least 4,000 lawsuits and claims still pending regarding VTE related to drospirenone. This is in addition to around 10,000 claims that Bayer has already settled without admitting liability. These claims of VTE have amounted to US$1.97 billion. Bayer also reached a settlement for arterial thromboembolic events, including

stroke Stroke is a medical condition in which poor cerebral circulation, blood flow to a part of the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemor ...

and

heart attack A myocardial infarction (MI), commonly known as a heart attack, occurs when Ischemia, blood flow decreases or stops in one of the coronary arteries of the heart, causing infarction (tissue death) to the heart muscle. The most common symptom ...

s, for US$56.9 million.

Research

A combination of ethinylestradiol, drospirenone, and prasterone is under development by Pantarhei Bioscience as a combined birth control pill for prevention of pregnancy in women. It includes prasterone (dehydroepiandrosterone; DHEA), an oral androgen prohormone, to replace testosterone and avoid testosterone deficiency caused by suppression of testosterone by ethinylestradiol and drospirenone. As of August 2018, the formulation is in phase II/III

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

s. Drospirenone has been suggested for potential use as a progestin in male hormonal contraception. Drospirenone has been studied in forms for parenteral administration.