Chlormadinone acetate, cyproterone acetate and dienogest are potent, orally active progestogens, which have antiandrogenic instead of partial androgenic activity. They act mainly by blocking androgen receptors in target organs, but also reduce the activity of skin 5alpha-reductase, the enzyme responsible for converting testosterone to the more potent androgen, 5alpha-dihydrotestosterone, in sebaceous glands and hair follicles. Chlormadinone acetate and cyproterone acetate also suppress gonadotropin secretion, thereby reducing ovarian and adrenal androgen production. Combined oral contraceptives (COCs) containing antiandrogenic progestogens provide highly effective contraception (gross and adjusted Pearl indices: 0-0.7 and 0-0.3, respectively) with excellent cycle control. Furthermore, COCs containing 2mg of chlormadinone acetate or cyproterone acetate plus 30 or 35 microg of ethinylestradiol produced improvement or resolution of seborrhoea in 80% of users, acne in 59-70%, hirsutism in 36% and androgen-related alopecia in up to 86%. These COCs are generally well tolerated, the main adverse effects being nonspecific or as expected for a COC (headache, breast tenderness and nausea). They have no clinically relevant effects on metabolic or liver functions or on bodyweight. Effects on mood and libido are uncommon (<3.5% and <6% of women, respectively). COCs containing antiandrogenic progestogens are likely to be particularly valuable in women with pre-existing androgen-related disorders who require contraception. They also increase the choice of products available for women with normal skin and hair who are concerned about the possibility of developing seborrhoea or acne with other COCs.

In women undergoing in-vitro fertilization, a sufficient vitamin D level (≥30 ng/ml) should be obtained. Vitamin D supplementation might improve metabolic parameters in women with PCOS. A high vitamin D intake might be protective against endometriosis.

ObjectiveTo evaluate the association between androstenedione, testosterone, and free testosterone and metabolic disturbances in polycystic ovary syndrome.MethodsWe analyzed the association between androstenedione, testosterone, and free testosterone and metabolic parameters in a cross-sectional study including 706 polycystic ovary syndrome and 140 BMI-matched healthy women. Polycystic ovary syndrome women were categorized into 4 groups: normal androstenedione and normal free testosterone (NA/NFT), elevated androstenedione and normal free testosterone (HA/NFT), normal androstenedione and elevated free testosterone (NA/HFT), elevated androstenedione and free testosterone (HA/HFT).ResultsPolycystic ovary syndrome women with elevated free testosterone levels (HA/HFT and NA/HFT) have an adverse metabolic profile including 2 h glucose, HbA1c, fasting and 2 h insulin, area under the insulin response curve, insulin resistance, insulin sensitivity index (Matsuda), triglycerides, total and high density lipoprotein cholesterol levels compared to NA/NFT (p<0.05 for all age- and BMI-adjusted analyses). In binary logistic regression analysis adjusted for age and BMI, odds ratio for insulin resistance was 2.78 (1.34–5.75, p = 0.006) for polycystic ovary syndrome women with HA/HFT compared to NA/NFT. We found no significantly increased risk of metabolic disorders in polycystic ovary syndrome women with HA/NFT. In multiple linear regression analyses (age- and BMI-adjusted), we found a significant negative association between androstenedione/free testosterone-ratio and area under the insulin response curve, insulin resistance, and total cholesterol/high density lipoprotein cholesterol-ratio and a positive association with Matsuda-index, and high density lipoprotein cholesterol (p<0.05 for all).ConclusionsPolycystic ovary syndrome women with elevated free testosterone levels but not with isolated androstenedione elevation have an adverse metabolic phenotype. Further, a higher androstenedione/free testosterone-ratio was independently associated with a beneficial metabolic profile.