Effects of a low-dose estrogen-antiandrogen combination (Diane-35) on clinical signs of androgenization, hormone profile and ovarian size in patients with polycystic ovary syndrome

Abstract

This study evaluates the effect of an oral contraceptive containing 35 micrograms of ethinyl estradiol and 2 mg of cyproterone acetate (Diane-35) on hormone dynamics, clinical signs of androgenization and ovarian size in patients with polycystic ovary syndrome (PCOS). Forty-six patients with PCOS were treated with Diane-35 for between 9 and 30 cycles without interruption (a total of 688 cycles). Clinical and hormonal evaluations were performed before treatment and every 3rd cycle during the treatment period while ultrasonographic assessment of ovaries was carried out every 6th cycle. A highly significant decrease in the LH/FSH ratio (p less than 0.001) as well as testosterone levels (p less than 0.001) was noticed after the 3rd cycle of Diane-35 administration. The mean serum androstenedione level decreased significantly (p less than 0.025) after the 3rd cycle, and showed a lowering trend thereafter. A significant reduction in serum DHEA-S levels was observed after the 6th cycle of treatment and they also showed a subsequent lowering trend. A highly significant increase in SHBG concentrations (p less than 0.001) was noticed after the 3rd cycle. Most of the patients noticed improvement in hirsutism between the 8th and 12th cycles of treatment. Mean ovarian size decreased significantly (p less than 0.001) after the 6th cycle, the normal size being reached after the 12th cycle of treatment. After the 4th cycle treatment was discontinued in 1 patient due to secondary amenorrhea, and in another 3 patients because of an increase in diastolic blood pressure. In a few patients side-effects such as weight gain, breast tenderness and mood changes in mild form were reported. Three out of 7 patients conceived in the 2nd or 3rd cycle after discontinuing Diane-35 therapy. The results of this study show that a combination of low-dose estrogen and cyproterone acetate (Diane-35) successfully reduces the hormonal disturbances which characterize PCOS. Apart from the normalization of the hormonal profile and the decrease in ovarian size, beneficial effects of Diane-35 were also observed on acne, hirsutism and regulation of the menstrual cycle. Favourable effects were also seen in terms of the pregnancy rate after discontinuation of Diane-35 therapy.

Polycystic ovary syndrome--from gynaecological curiosity to multisystem endocrinopathy

“…Cyproterone acetate is a synthetic progesterone with both antigonadotrophic and antiandrogenic effects, giving it an advantage for the treatment of PCOS over the majority of progestins in oral contraceptives. Its combination with ethinyl oestradiol has been successful in suppressing hyperandrogenism, resulting in improvement of clinical signs and normalization of the hormonal disturbances which characterize PCOS (Prelevic et al, 1989). The efficacy of this treatment is due to the antiandrogenic activity at androgen receptor level, suppression of serum LH and ovarian androgen concentrations, reduction in 5-reductase concentrations, increased metabolic clearance of testosterone and increase in SHBG concentration.…”

Risks, benefits size and clinical implications of combined oral contraceptive use in women with polycystic ovary syndrome

“…The size of the SHBG increase found with this combination ranged from 37.31 nmol/l to 179.01 nmol/l, with an average increase of 141.7 nmol/l ( p = 0.002). It has been accepted that the combination induces the highest rise in SHBG and that is the most estrogenic COC in relation to its higher contents of estrogen and to the low androgenicity of CPA [ 56 , 64 ]. Therefore, if the primary outcome is to increase SHBG, it was shown that 2 mg CPA had no counteractive effect on the increase of SHBG levels induced by EE.…”

Unwanted Body Hair and Its Removal: A Review

“…18 Oral contraceptives suppress adrenal and ovarian androgen production while cyproterone acetate competitively inhibits the binding of testosterone and dihydrotestosterone (DHT) to specific intracellular androgen receptors, and directly inhibits 5 ␣ -reductase, which mediates the transformation of testosterone to DHT. 19,20 Nevertheless, 50% of these patients still suffered from hirsutism after 18 months of treatment and 25% after 36 months of treatment. 19,20 Nevertheless, 50% of these patients still suffered from hirsutism after 18 months of treatment and 25% after 36 months of treatment.…”

“…Improvement in hirsutism has been documented in patients with polycystic ovary disease 8 to 12 months after treatment with Dianette. 19,20 Nevertheless, 50% of these patients still suffered from hirsutism after 18 months of treatment and 25% after 36 months of treatment. 21 Barth et al 22 found that higher doses of cyproterone acetate (20 mg or 100 mg) produced a faster initial response than lower doses (2 mg), but the effects leveled off such that no difference in clinical efficacy was noted at 12 months.…”