A review of the cardiovascular and breast actions of drospirenone in preclinical studies

Abstract

Objective Hormone therapy is effective for the relief of menopausal symptoms. For women with a uterus, addition of a progestogen is required to protect the endometrium. However, synthetic progestins differ in certain pharmacological characteristics that may have implications for clinical practice. This literature-based review explores differences in the preclinical and clinical profiles of the progestins used in hormone therapy, focusing on their effects on the cardiovascular system and breast.

Design Studies included are selected based on criteria of relevance, topicality, and subjective assessment of quality, following comprehensive searches of online databases.

Results The biological actions of progestins depend on their receptor binding affinity profiles as well as their specific effects on progesterone receptor signaling, which often differ based on the ligand. Observational studies indicate that hormone therapies which include medroxyprogesterone acetate and certain other progestins may attenuate the cardiovascular benefits of estrogen and add to risk of breast cancer. Appraisal of the evidence suggests these clinical effects correlate with the progestin's pharmacological profile. Among the newer progestins, drospirenone has been investigated extensively in preclinical studies. With a pharmacological profile similar to progesterone, drospirenone is devoid of estrogenic, androgenic and glucocorticoid activity and possesses potent antialdosterone and antiandrogenic activity. This profile of drospirenone contrasts with that of older progestins, conferring specific effects on cardiovascular and breast cells.

Conclusions The relative risks associated with hormone therapy vary with the combination of hormones included. Differences in pharmacological profile among progestins may translate to characteristic divergences in clinical profile, with potential implications for long-term health.

Key words:

• DROSPIRENONE
• PROGESTINS
• MENOPAUSE
• CARDIOVASCULAR SYSTEM
• BREAST

Acknowledgement

Editorial support to the authors in the preparation of this review was provided by Parexel MMS.

Conflict of interest  Both authors [T.S. and A.R.G.] have received occasional honoraria for public presentations and consulting activity for companies selling products for menopausal health, including Bayer Schering Pharma, the manufacturer of drospirenone.

Source of funding  The authors received neither funding nor compensation for independently writing the manuscript. Parexel MMS received funding from Bayer Schering Pharma, the manufacturer of drospirenone, to provide editorial assistance.