Pharmacological and metabolic effects of drospirenone as a progestin-only pill compared to combined formulations with estrogen.

The spironolactone derivative drospirenone is combined with ethinylestradiol or estetrol in combined oral contraceptives. Formulations with 17-ß-estradiol are used to treat climacteric symptoms. A drospirenone-only formulation has been introduced for contraception. Here, the pharmacological properties of drospirenone, the impact of the different formulations on metabolic and laboratory parameters, and the resulting clinical implications are reviewed. Ethinylestradiol, an inhibitor of CYP metabolic enzymes, changes the pharmacokinetics of drospirenone, leading to a higher drospirenone exposure with ethinylestradiol/drospirenone compared to the drospirenone-only preparation. In addition, several metabolic alterations have been described. The impact of estetrol is less pronounced, and for 17-ß-estradiol/drospirenone and drospirenone-only, decreased triglyceride and cholesterol levels were observed. Ethinylestradiol induces various pro-coagulatory factors, leading to hypercoagulability. The effect is significantly reduced with estetrol, and no influence was observed with the drospirenone-only preparation. The anti-mineralocorticoid activity of drospirenone seems to positively counteract the renin-angiotensin-aldosterone-system-activating action of ethinylestradiol. There is no influence on blood pressure with ethinylestradiol/drospirenone and estetrol/drospirenone formulations, while in clinical trials, a reduction has been observed with 17-ß-estradiol/drospirenone and drospirenone-only. Anti-aldosterone activity via non-renal mineralocorticoid receptors is associated with cardiovascular health, while interactions with parathyroid hormone signaling impact bone structure and vascular calcification. Though the clinical relevance is unclear for drospirenone, data in this context are reviewed. To sum up, the advantages of drospirenone in hormonal contraception and treatment of menopausal symptoms have been demonstrated for all the formulations described here. Combination with estrogen confers benefits and risks, which must be considered.

PCOS: A Chronic Disease That Fails to Produce Adequately Specialized Pro-Resolving Lipid Mediators (SPMs).

INTRODUCTION: Polycystic ovary syndrome (PCOS) is an endocrinological disorder that affects 5-15% of women of their reproductive age and is a frequent cause of infertility. Major symptoms include hyperandrogenism, ovulatory dysfunction, and often obesity and/or insulin resistance. PCOS also represents a state of chronic low-grade inflammation that is closely interlinked with the metabolic features. "Classical" pro-inflammatory lipid mediators such as prostaglandins (PG), leukotrienes (LT), or thromboxanes (TX) are derived from arachidonic acid (AA) and are crucial for the initial response. Resolution processes are driven by four families of so-called specialized pro-resolving mediators (SPMs): resolvins, maresins, lipoxins, and protectins. The study aimed to establish lipid mediator profiles of PCOS patients compared to healthy women to identify differences in their resolutive and pro-inflammatory lipid parameters. MATERIAL AND METHODS: Fifteen female patients (18-45 years) were diagnosed with PCOS according to Rotterdam criteria, and five healthy women, as a comparator group, were recruited for the study. The main outcome measures were: pro-inflammatory lipid mediators (PG, LT, TX) and their precursor AA, SPMs (resolvins, maresins, protectins, lipoxins), their precursors EPA, DHA, DPA, and their active biosynthesis pathway intermediates (18-HEPE, 17-HDHA, 14-HDHA). RESULTS: The level of pro-inflammatory parameters in serum was significantly higher in PCOS-affected women. The ratio (sum of pro-inflammatory molecules)/(sum of SPMs plus hydroxylated intermediates) reflecting the inflammatory state was significantly lower in the group of healthy women. CONCLUSION: There is a strong pro-inflammatory state in PCOS patients. Further research will clarify whether supplementation with SPMs or their precursors may improve this state.