Drospirenone was patented in 1976 and introduced for medical use in 2000.[14][15] It is available widely throughout the world.[9] The medication is sometimes referred to as a "fourth-generation" progestin.[16][17] It is available as a
generic medication.[18] In 2020, a formulation of drospirenone with
ethinylestradiol was the 145th most commonly prescribed medication in the United States, with more than 4million prescriptions.[19][20]
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).[51] The incidence is about 4-fold higher on average than in women not taking a birth control pill.[51] 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.[52][53] The risk of VTE during
pregnancy is 5 to 20 in 10,000 women per year and during the
postpartum period is 40 to 65 per 10,000 women per year.[53] 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.[11] In contrast to ethinylestradiol-containing birth control pills, neither
progestogen-only birth control nor the combination of
transdermalestradiol and an oral progestin in
menopausal hormone therapy is associated with an increased risk of VTE.[11][54]
Different progestins in ethinylestradiol-containing birth control pills have been associated with different risks of VTE.[11] Birth control pills containing progestins such as
desogestrel,
gestodene, drospirenone, and
cyproterone acetate 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–controlobservational studies.[11][52] However, this area of research is controversial, and
confounding factors may have been present in these studies.[11][52][55] 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.[11][52][55][56] These kinds of observational studies have certain advantages over the aforementioned types of studies, like better ability to control for confounding factors.[56]Systematic reviews and
meta-analyses 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.[57][58][52]
Androgenic progestins have been found to antagonize to some degree the effects of ethinylestradiol on coagulation.[59][60][61][62] As a result, more androgenic progestins, like levonorgestrel and
norethisterone, may oppose the procoagulatory effects of ethinylestradiol and result in a lower increase in risk of VTE.[11][63] 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.[11][63]
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.[49]
Data on risk of
breast cancer in women with newer progestins like drospirenone are lacking at present.[69] Progestogen-only birth control is not generally associated with a higher risk of breast cancer.[69] Conversely, combined birth control and menopausal hormone therapy with an estrogen and a progestogen are associated with higher risks of breast cancer.[70][69][71]
Overdose
These have been no reports of serious
adverse effects with
overdose of drospirenone.[3] Symptoms that may occur in the event of an overdose may include
nausea,
vomiting, and
vaginal bleeding.[3] There is no
antidote for overdose of drospirenone and treatment of overdose should be based on
symptoms.[3] Since drospirenone has antimineralocorticoid activity, levels of
potassium and
sodium should be measured and signs of
metabolic acidosis should be monitored.[3]
Drospirenone is an
antagonist of the MR, the
biological target of
mineralocorticoids like
aldosterone, and hence is an antimineralocorticoid.[72] 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.[1][4][74][65] Drospirenone is about 5.5 to 11 times more potent as an antimineralocorticoid than
spironolactone in animals.[72][78][85] Accordingly, 3 to 4 mg drospirenone is said to be equivalent to about 20 to 25 mg spironolactone in terms of antimineralocorticoid activity.[86][3] It has been said that the
pharmacological profile of drospirenone more closely resembles that of progesterone than other progestins due to its antimineralocorticoid activity.[72] Drospirenone is the only clinically used progestogen with prominent antimineralocorticoid activity besides progesterone.[1] 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.[87] Both drospirenone and progesterone are actually weak
partial agonists of the MR in the absence of
mineralocorticoids.[5][4][65]
Drospirenone is an antagonist of the AR, the biological target of
androgens like
testosterone and
dihydrotestosterone (DHT).[1][4] It has about 1 to 65% of the affinity of the synthetic
anabolic steroidmetribolone for the AR.[1][4][5][65] The medication is more potent as an antiandrogen than
spironolactone, but is less potent than
cyproterone acetate, with about 30% of its antiandrogenic activity in animals.[1][91][72][78] Progesterone displays antiandrogenic activity in some assays similarly to drospirenone,[4] although this issue is controversial and many researchers regard progesterone as having no significant antiandrogenic activity.[92][1][5]
Drospirenone shows antiandrogenic effects on the
serumlipid profile, including higher
HDLcholesterol and
triglyceride levels and lower
LDL cholesterol levels, at a dose of 3 mg/day in women.[4] 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.[4][1][77] 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.[93]Androgenic 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.[11][63][59][60][61][62]
The
oralbioavailability of drospirenone is between 66 and 85%.[1][4][5]Peak levels occur 1 to 6 hours after an oral dose.[1][4][3][85] Levels are about 27 ng/mL after a single 4 mg dose.[3] 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.[1][3][4] Peak levels of drospirenone at steady state with 4 mg/day drospirenone are about 41 ng/mL.[3] 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.[4][1] The
pharmacokinetics of oral drospirenone are linear with a single dose across a dose range of 1 to 10 mg.[3][4] Intake of drospirenone with
food does not influence the
absorption of drospirenone.[3]
Drospirenone is
excreted in
urine and
feces, with slightly more excreted in feces than in urine.[3] Only trace amounts of unchanged drospirenone can be found in urine and feces.[3] At least 20 different
metabolites can be identified in urine and feces.[4] Drospirenone and its metabolites are excreted in urine about 38% as
glucuronideconjugates, 47% as
sulfate conjugates, and less than 10% in unconjugated form.[4] In feces, excretion is about 17% glucuronide conjugates, 20% sulfate conjugates, and 33% unconjugated.[4]
The
elimination half-life of drospirenone is between 25 and 33 hours.[3][4][1] The half-life of drospirenone is unchanged with repeated administration.[3] Elimination of drospirenone is virtually complete 10 days after the last dose.[4][3]
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
syntheticsteroidal17α-spirolactone, or more simply a spirolactone.[9][95] It is an
analogue of other spirolactones like
spironolactone,
canrenone, and
spirorenone.[9][95] Drospirenone differs structurally from spironolactone only in that the C7α
acetylthiosubstitution of spironolactone has been removed and two
methylene groups have been substituted in at the C6β–7β and C15β–16β positions.[96]
Spirolactones like drospirenone and spironolactone are
derivatives of
progesterone, which likewise has progestogenic and antimineralocorticoid activity.[97][98][99] The loss of the C7α acetylthio group of spironolactone, a compound with negligible progestogenic activity,[100][101] 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.[102]
History
Drospirenone was patented in 1976 and introduced for medical use in 2000.[14][15]Schering AG of
Germany has been granted several patents on the production of drospirenone, including WIPO and US patents, granted in 1998 and 2000, respectively.[103][104] It was introduced for medical use in combination with
ethinylestradiol as a
combined birth control pill in 2000.[14] Drospirenone is sometimes described as a "fourth-generation" progestin based on its time of introduction.[16][17] The medication was approved for use in
menopausal hormone therapy in combination with
estradiol in 2005.[23] Drospirenone was introduced for use as a
progestogen-only birth control pill in 2019.[3] A combined birth control pill containing
estetrol and drospirenone was approved in 2021.[105]
Society and culture
Generic names
Drospirenone is the
generic name of the drug and its
INNTooltip International Nonproprietary Name,
USANTooltip United States Adopted Name,
BANTooltip British Approved Name, and
JANTooltip Japanese Accepted Name, while drospirénone is its
DCFTooltip Dénomination Commune Française.[9] Its name is a shortened form of the name 1,2-dihydrospirorenone or dihydrospirenone.[9][95] 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).[9][95][106][107][108][109][105]
Brand names
Drospirenone is marketed in combination with an estrogen under a variety of brand names throughout the world.[9] 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.[9][105]
Drospirenone is marketed widely throughout the world.[9]
Generation
Drospirenone has been categorized as a "fourth-generation" progestin.[65]
Litigation
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.[55]
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.[110] 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.[110]
As of 17 July 2015, there have been at least 4,000 lawsuits and claims still pending regarding VTE related to drospirenone.[111] This is in addition to around 10,000 claims that Bayer has already settled without admitting liability.[111] These claims of VTE have amounted to US$1.97 billion.[111] Bayer also reached a settlement for
arterial thromboembolic events, including
stroke and
heart attacks, for US$56.9 million.[111]
^Gaspard U, Endrikat J, Desager JP, Buicu C, Gerlinger C, Heithecker R (April 2004). "A randomized study on the influence of oral contraceptives containing ethinylestradiol combined with drospirenone or desogestrel on lipid and lipoprotein metabolism over a period of 13 cycles". Contraception. 69 (4): 271–278.
doi:
10.1016/j.contraception.2003.11.003.
PMID15033400.
^Torgerson DJ, Bell-Syer SE (June 2001). "Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials". JAMA. 285 (22): 2891–2897.
doi:
10.1001/jama.285.22.2891.
PMID11401611.
S2CID25078579.
^
abWhitehead M (March 2006). "Hormone replacement therapy with estradiol and drospirenone: an overview of the clinical data". The Journal of the British Menopause Society. 12 (Suppl 1): 4–7.
doi:
10.1258/136218006775992185.
PMID16513012.
S2CID38095916.
^Lanza di Scalea T, Pearlstein T (June 2017). "Premenstrual Dysphoric Disorder". The Psychiatric Clinics of North America. 40 (2): 201–216.
doi:
10.1016/j.psc.2017.01.002.
PMID28477648.
^
abcBayer (25 March 2013).
"Summary of Product Characteristics (SPC): Yasmin". London: electronic Medicines Compendium (eMC), Datapharm. Retrieved 24 April 2014. 4.3. Contraindications: • Severe chronic kidney disease or acute kidney failure. • Presence or history of severe hepatic disease as long as liver function values have not returned to normal.
^
abBayer (10 April 2012).
"Yasmin full prescribing information"(PDF). Silver Spring, Md.: Food and Drug Administration (FDA). Retrieved 14 April 2012. 4. Contraindications: • Renal impairment. • Adrenal insufficiency. • Liver disease.
^Nelson AL, Cwiak C (2011). "Combined oral contraceptives (COCs)". In Hatcher RA, Trussell J, Nelson AL, Cates Jr W, Kowal D, Policar MS (eds.). Contraceptive Technology (20th revised ed.). New York: Ardent Media. pp. 249–341.
ISBN978-1-59708-004-0.
ISSN0091-9721.
OCLC781956734.
^Oedingen C, Scholz S, Razum O (May 2018). "Systematic review and meta-analysis of the association of combined oral contraceptives on the risk of venous thromboembolism: The role of the progestogen type and estrogen dose". Thrombosis Research. 165: 68–78.
doi:
10.1016/j.thromres.2018.03.005.
PMID29573722.
^
abWiegratz I, Kuhl H (September 2006). "Metabolic and clinical effects of progestogens". The European Journal of Contraception & Reproductive Health Care. 11 (3): 153–161.
doi:
10.1080/13625180600772741.
PMID17056444.
S2CID27088428.
^
abSitruk-Ware R, Nath A (February 2013). "Characteristics and metabolic effects of estrogen and progestins contained in oral contraceptive pills". Best Practice & Research. Clinical Endocrinology & Metabolism. 27 (1): 13–24.
doi:
10.1016/j.beem.2012.09.004.
PMID23384742.
^
abcFarris M, Bastianelli C, Rosato E, Brosens I, Benagiano G (October 2017). "Pharmacodynamics of combined estrogen-progestin oral contraceptives: 2. effects on hemostasis". Expert Review of Clinical Pharmacology. 10 (10): 1129–1144.
doi:
10.1080/17512433.2017.1356718.
PMID28712325.
S2CID205931204.
^
abSimoncini T, Genazzani AR (February 2010). "A review of the cardiovascular and breast actions of drospirenone in preclinical studies". Climacteric. 13 (1): 22–33.
doi:
10.3109/13697130903437375.
PMID19938948.
S2CID4306359.
^Fuhrmann U, Krattenmacher R, Slater EP, Fritzemeier KH (October 1996). "The novel progestin drospirenone and its natural counterpart progesterone: biochemical profile and antiandrogenic potential". Contraception. 54 (4): 243–251.
doi:
10.1016/S0010-7824(96)00195-3.
PMID8922878.
^
abHapgood JP, Africander D, Louw R, Ray RM, Rohwer JM (July 2014). "Potency of progestogens used in hormonal therapy: toward understanding differential actions". The Journal of Steroid Biochemistry and Molecular Biology. 142: 39–47.
doi:
10.1016/j.jsbmb.2013.08.001.
PMID23954501.
S2CID12142015.
^Bastianelli C, Farris M, Rosato E, Brosens I, Benagiano G (November 2018). "Pharmacodynamics of combined estrogen-progestin oral contraceptives 3. Inhibition of ovulation". Expert Review of Clinical Pharmacology. 11 (11): 1085–1098.
doi:
10.1080/17512433.2018.1536544.
PMID30325245.
S2CID53246678.
^Endrikat J, Gerlinger C, Richard S, Rosenbaum P, Düsterberg B (December 2011). "Ovulation inhibition doses of progestins: a systematic review of the available literature and of marketed preparations worldwide". Contraception. 84 (6): 549–557.
doi:
10.1016/j.contraception.2011.04.009.
PMID22078182.
^Nieschlag E, Behre HM (2012). "The essential role of testosterone in hormonal male contraception". In Nieschlag E, Behre HM, Nieschlag S (eds.). Testosterone. Cambridge University Press. pp. 470–493.
doi:
10.1017/CBO9781139003353.023.
ISBN978-1-139-00335-3.
^
abStanczyk FZ (2007). "Structure –Function Relationships, Pharmacokinetics, and Potency of Orally and Parenterally Administered Progestogens". Treatment of the Postmenopausal Woman. Academic Press. pp. 779–798.
doi:
10.1016/B978-012369443-0/50067-3.
ISBN978-0-12-369443-0.
^Ménard J (March 2004). "The 45-year story of the development of an anti-aldosterone more specific than spironolactone". Molecular and Cellular Endocrinology. 217 (1–2): 45–52.
doi:
10.1016/j.mce.2003.10.008.
PMID15134800.
S2CID19701784. [Spironolactone] was synthesized after the demonstration of the natriuretic effect of progesterone (Landau et al., 1955).
^Aldosterone. Elsevier Science. 23 January 2019. p. 46.
ISBN978-0-12-817783-9. In addition to spironolactone, which is a derivative of progesterone [...]
^Hu X, Li S, McMahon EG, Lala DS, Rudolph AE (August 2005). "Molecular mechanisms of mineralocorticoid receptor antagonism by eplerenone". Mini Reviews in Medicinal Chemistry. 5 (8): 709–718.
doi:
10.2174/1389557054553811.
PMID16101407.
^Nakajima ST, Brumsted JR, Riddick DH, Gibson M (July 1989). "Absence of progestational activity of oral spironolactone". Fertility and Sterility. 52 (1): 155–158.
doi:
10.1016/s0015-0282(16)60807-5.
PMID2744183.
^Hertz R, Tullner WW (November 1958). "Progestational activity of certain steroid-17-spirolactones". Proceedings of the Society for Experimental Biology and Medicine. 99 (2): 451–452.
doi:
10.3181/00379727-99-24380.
PMID13601900.
S2CID20150966.
^WO patent 9806738, Mohr, Jörg-Thorsten & Nickisch, Klaus, "PROCESS FOR PRODUCING DROSPIRENONE (6ss,7ss;15ss,16ss-DIMETHYLENE-3-OXO-17 alpha -PREGN-4-EN-21,17-CARBOLACTONE, DRSP), AS WELL AS 7 alpha -(3-HYDROXY-1-PROPYL)-6ss,7ss;15ss,16ss-DIMETHYLENE-5ss-ANDROSTANE-3ss,5,17ss-TRIOL (ZK 92836) AND 6ss,7ss;15ss,16ss-DIMETHYLENE-5ss HYDROXY-5-OXO-17 alpha -ANDROSTANE-21, 17-CARBOLACTONE", issued 1998-02-19, assigned to Shering AG
^US patent 6121465, Mohr, Joerg-Thorston & Nickisch, Klaus, "Process for production drospirenone and intermediate products of the process", issued 2000-09-19, assigned to Scheiring AG and Bayer Schering Pharma
^Nippe S, General S (September 2011). "Parenteral oil-based drospirenone microcrystal suspensions-evaluation of physicochemical stability and influence of stabilising agents". International Journal of Pharmaceutics. 416 (1): 181–188.
doi:
10.1016/j.ijpharm.2011.06.036.
PMID21729745.
^Nippe S, General S (November 2012). "Combination of injectable ethinyl estradiol and drospirenone drug-delivery systems and characterization of their in vitro release". European Journal of Pharmaceutical Sciences. 47 (4): 790–800.
doi:
10.1016/j.ejps.2012.08.009.
PMID22940138.
^Nippe S, Preuße C, General S (February 2013). "Evaluation of the in vitro release and pharmacokinetics of parenteral injectable formulations for steroids". European Journal of Pharmaceutics and Biopharmaceutics. 83 (2): 253–265.
doi:
10.1016/j.ejpb.2012.09.006.
PMID23116659.
^Nippe S, General S (April 2015). "Investigation of injectable drospirenone organogels with regard to their rheology and comparison to non-stabilized oil-based drospirenone suspensions". Drug Development and Industrial Pharmacy. 41 (4): 681–691.
doi:
10.3109/03639045.2014.895375.
PMID24621345.
S2CID42932558.
Archer DF (February 2007). "Drospirenone-containing hormone therapy for postmenopausal women. Perspective on current data". The Journal of Reproductive Medicine. 52 (2 Suppl): 159–164.
PMID17477110.
Archer DF (2007). "Drospirenone, a progestin with added value for hypertensive postmenopausal women". Menopause. 14 (3 Pt 1): 352–354.
doi:
10.1097/gme.0b013e31804d440b.
PMID17414576.
Bitzer J, Paoletti AM (2009). "Added benefits and user satisfaction with a low-dose oral contraceptive containing drospirenone: results of three multicentre trials". Clinical Drug Investigation. 29 (2): 73–78.
doi:
10.2165/0044011-200929020-00001.
PMID19133702.
S2CID10356578.
Dickerson V (November 2002). "Quality of life issues. Potential role for an oral contraceptive containing ethinyl estradiol and drospirenone". The Journal of Reproductive Medicine. 47 (11 Suppl): 985–993.
PMID12497673.
Fenton C, Wellington K, Moen MD, Robinson DM (2007). "Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris". Drugs. 67 (12): 1749–1765.
doi:
10.2165/00003495-200767120-00007.
PMID17683173.
S2CID46976925.
Han L, Jensen JT (October 2014). "Expert opinion on a flexible extended regimen of drospirenone/ethinyl estradiol contraceptive". Expert Opinion on Pharmacotherapy. 15 (14): 2071–2079.
doi:
10.1517/14656566.2014.949237.
PMID25186109.
S2CID25338932.
Idota N, Kobayashi M, Miyamori D, Kakiuchi Y, Ikegaya H (March 2015). "Drospirenone detected in postmortem blood of a young woman with pulmonary thromboembolism: A case report and review of the literature". Legal Medicine. 17 (2): 109–115.
doi:
10.1016/j.legalmed.2014.10.001.
PMID25454533.
Krattenmacher R (July 2000). "Drospirenone: pharmacology and pharmacokinetics of a unique progestogen". Contraception. 62 (1): 29–38.
doi:
10.1016/S0010-7824(00)00133-5.
PMID11024226.
Lete I, Chabbert-Buffet N, Jamin C, Lello S, Lobo P, Nappi RE, et al. (2015). "Haemostatic and metabolic impact of estradiol pills and drospirenone-containing ethinylestradiol pills vs. levonorgestrel-containing ethinylestradiol pills: A literature review". The European Journal of Contraception & Reproductive Health Care. 20 (5): 329–343.
doi:
10.3109/13625187.2015.1050091.
PMID26007631.
S2CID41601833.
Li J, Ren J, Sun W (March 2017). "A comparative systematic review of Yasmin (drospirenone pill) versus standard treatment options for symptoms of polycystic ovary syndrome". European Journal of Obstetrics, Gynecology, and Reproductive Biology. 210: 13–21.
doi:
10.1016/j.ejogrb.2016.11.013.
PMID27923166.
Motivala A, Pitt B (2007). "Drospirenone for oral contraception and hormone replacement therapy: are its cardiovascular risks and benefits the same as other progestogens?". Drugs. 67 (5): 647–655.
doi:
10.2165/00003495-200767050-00001.
PMID17385938.
S2CID22985078.
Oelkers W (December 2002). "Antimineralocorticoid activity of a novel oral contraceptive containing drospirenone, a unique progestogen resembling natural progesterone". The European Journal of Contraception & Reproductive Health Care. 7 (Suppl 3): 19–26, discussion 42–3.
PMID12659403.
Oelkers W (December 2000). "Drospirenone--a new progestogen with antimineralocorticoid activity, resembling natural progesterone". The European Journal of Contraception & Reproductive Health Care. 5 (Suppl 3): 17–24.
doi:
10.1080/14730782.2000.12288986.
PMID11246598.
S2CID35051390.
Oelkers W (March 2004). "Drospirenone, a progestogen with antimineralocorticoid properties: a short review". Molecular and Cellular Endocrinology. 217 (1–2): 255–261.
doi:
10.1016/j.mce.2003.10.030.
PMID15134826.
S2CID19936032.
Rapkin RB, Creinin MD (October 2011). "The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium". Expert Opinion on Pharmacotherapy. 12 (15): 2403–2410.
doi:
10.1517/14656566.2011.610791.
PMID21877996.
S2CID40231903.
Rübig A (October 2003). "Drospirenone: a new cardiovascular-active progestin with antialdosterone and antiandrogenic properties". Climacteric. 6 (Suppl 3): 49–54.
PMID15018248.
Sehovic N, Smith KP (May 2010). "Risk of venous thromboembolism with drospirenone in combined oral contraceptive products". The Annals of Pharmacotherapy. 44 (5): 898–903.
doi:
10.1345/aph.1M649.
PMID20371756.
S2CID8248469.
Shulman LP (June 2006). "A review of drospirenone for safety and tolerability and effects on endometrial safety and lipid parameters contrasted with medroxyprogesterone acetate, levonorgestrel, and micronized progesterone". Journal of Women's Health. 15 (5): 584–590.
doi:
10.1089/jwh.2006.15.584.
PMID16796485.
Simoncini T, Genazzani AR (February 2010). "A review of the cardiovascular and breast actions of drospirenone in preclinical studies". Climacteric. 13 (1): 22–33.
doi:
10.3109/13697130903437375.
PMID19938948.
S2CID4306359.
Thorneycroft IH (November 2002). "Evolution of progestins. Focus on the novel progestin drospirenone". The Journal of Reproductive Medicine. 47 (11 Suppl): 975–980.
PMID12497671.
Toni I, Neubert A, Botzenhardt S, Gratzki N, Rascher W (September 2013). "Venous thromboembolism in adolescents associated with drospirenone-containing oral contraceptives - two case reports". Klinische Padiatrie. 225 (5): 266–267.
doi:
10.1055/s-0033-1353169.
PMID23975850.
S2CID19085818.
Whitehead M (March 2006). "Hormone replacement therapy with estradiol and drospirenone: an overview of the clinical data". The Journal of the British Menopause Society. 12 (Suppl 1): 4–7.
doi:
10.1258/136218006775992185.
PMID16513012.
S2CID38095916.
Zhao X, Zhang XF, Zhao Y, Lin X, Li NY, Paudel G, et al. (September 2016). "Effect of combined drospirenone with estradiol for hypertensive postmenopausal women: a systemic review and meta-analysis". Gynecological Endocrinology. 32 (9): 685–689.
doi:
10.1080/09513590.2016.1183629.
PMID27176003.
S2CID9116138.