Drospirenone is a progestin and antiandrogen medication which is used in birth control pills to prevent pregnancy and in menopausal hormone therapy, among other uses.
[1][4] Common side effects include acne, headache, breast tenderness, weight increase, and menstrual changes.
[4] Rare side effects may include high potassium levels and blood clots (when taken as a combined oestrogen-progestogen pill), among others.
[19] In 2020, a formulation of drospirenone with ethinylestradiol was the 145th most commonly prescribed medication in the United States, with more than 4 million prescriptions.
[22][23] 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.
[28][29] Studies have found that EE/DRSP is superior to placebo in reducing premenstrual emotional and physical symptoms while also improving quality of life.
[33][34] Due to its antimineralocorticoid activity, drospirenone opposes estrogen-induced salt and water retention and maintains or slightly reduces body weight.
[35] Drospirenone is available in the following formulations, brand names, and indications:[36][37] Contraindications of drospirenone include renal impairment or chronic kidney disease, 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).
[4] Adverse effects of drospirenone alone occurring in more than 1% of women may include unscheduled menstrual bleeding (breakthrough or intracyclic) (40.3–64.4%), acne (3.8%), metrorrhagia (2.8%), headache (2.7%), breast pain (2.2%), weight gain (1.9%), dysmenorrhea (1.9%), nausea (1.8%), vaginal hemorrhage (1.7%), decreased libido (1.3%), breast tenderness (1.2%), and irregular menstruation (1.2%).
[49] In women with mild or moderate chronic kidney disease, or in combination with chronic daily use of other potassium-sparing medications (ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, heparin, antimineralocorticoids, or nonsteroidal anti-inflammatory drugs), a potassium level should be checked after two weeks of use to test for hyperkalemia.
[4] Birth control pills containing ethinylestradiol and a progestin are associated with an increased risk of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE).
[12][64] 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.
[50] Drospirenone has been found to stimulate the proliferation and migration of breast cancer cells in preclinical research, similarly to certain other progestins.
[67][68][69] Data on risk of breast cancer in women with newer progestins like drospirenone are lacking at present.
[70] Conversely, combined birth control and menopausal hormone therapy with an estrogen and a progestogen are associated with higher risks of breast cancer.
[4] Since drospirenone has antimineralocorticoid activity, levels of potassium and sodium should be measured and signs of metabolic acidosis should be monitored.
[4] Treatment for 10 days with 200 mg twice daily ketoconazole, 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.
[4] Drospirenone may interact with potassium-sparing medications such as ACE inhibitors, angiotensin II receptor antagonists, potassium-sparing diuretics, potassium supplements, heparin, antimineralocorticoids, and nonsteroidal anti-inflammatory drugs to further increase potassium levels.
[1][80][79] The medication acts as a contraceptive by activating the PR, which suppresses the secretion of luteinizing hormone, inhibits ovulation, and alters the cervical membrane and endometrium.
[1][82][5] 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.
[82] No studies of the antigonadotropic effects of drospirenone or its influence on hormone levels appear to have been conducted in men.
[87][4] It has been said that the pharmacological profile of drospirenone more closely resembles that of progesterone than other progestins due to its antimineralocorticoid activity.
[6][5][66] Due to its antimineralocorticoid activity, drospirenone increases natriuresis, decreases water retention and blood pressure, and produces compensatory increases in plasma renin activity as well as circulating levels and urinary excretion of aldosterone.
[5] Similar effects occur during the luteal phase of the menstrual cycle due to increased progesterone levels and the resulting antagonism of the MR.[5] Estrogens, particularly ethinylestradiol, activate liver production of angiotensinogen and increase levels of angiotensinogen and angiotensin II, thereby activating the renin–angiotensin–aldosterone system.
[5] Accumulating research indicates that antimineralocorticoids like drospirenone and spironolactone may also have positive effects on adipose tissue and metabolic health.
[12][64][60][61][62][63] Drospirenone stimulates the proliferation of MCF-7 breast cancer cells in vitro, an action that is independent of the classical PRs and is instead mediated via the progesterone receptor membrane component-1 (PGRMC1).
[95] It is unclear if these findings may explain the different risks of breast cancer observed with progesterone and progestins in clinical studies.
[66] Many lawsuits have been filed against 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.
[56] 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.
[112] Bayer also reached a settlement for arterial thromboembolic events, including stroke and heart attacks, for US$56.9 million.