A novel oestradiol--desogestrel preparation for hormone replacement therapy: effects on hormones, lipids, bone, climacteric symptoms and endometrium.

Desogestrel is a strong progestogen with low androgenicity which has so far been used only in oral contraceptives. We studied the feasibility of administering desogestrel in combination with oestradiol as hormone replacement therapy (HRT). Thirty women received a sequential combination containing 1.5 mg micronised oestradiol (24 days) and 0.15 mg desogestrel (last 12 days of cycle) for 6 months. At that stage 6 of the women dropped out; the remaining 24 were studied for a total of 12 months. The treatment alleviated vasomotor symptoms effectively in all the women and induced regular withdrawal bleeding in 86% of them. Secretory changes were observed in the endometria of 16 of the 20 women with adequate endometrial samples assessed after 12 months of treatment. No signs of hyperplasia or atypia were found. Six months of treatment resulted in a decrease in the mean serum follicle-stimulating-hormone concentration from 66.2 (+/- 4.3, S.E.M.) to 23.3 (+/- 3.1) IU/l and a rise in the oestradiol and sex-hormone-binding globulin concentrations from 87.9 (+/- 13.7) to 233.1 (+/- 20.4) pmol/l and from 52.1 (+/- 4.6) to 70.2 (+/- 5.6) nmol/l, respectively. Testosterone levels decreased. There were significant reductions in serum total and low density lipoprotein (LDL) cholesterol and triglycerides. After 12 months of treatment high-density lipoprotein (HDL) cholesterol values did not differ significantly from the pretreatment levels. The HDL/LDL and HDL/total cholesterol ratios increased. The treatment reduced bone turnover as indicated by decreases in bone alkaline phosphatase and osteocalcin serum levels and by lowered urinary calcium/creatinine and hydroxyproline/creatinine ratios. An increase of about 2% in forearm bone mineral density was also observed. This new oestradiol-desogestrel preparation therefore appears to be a promising alternative form of HRT. It alleviates climacteric symptoms effectively, exhibits favourable effects on serum lipids and lipoproteins and prevents bone loss.