Abstract
Most progestogens in oral contraceptives are testosterone derivatives and have androgenic side effects such as weight increase, acne and hirsutism. They pose a problem to many women just like the clinical picture of the polycystic ovary syndrome (PCO) with obesity, hirsutism, acne and amenorrhea.
The aim of this study was to evaluate androgenicity of the most used progestogens with special reference to desogestrel which is a new progestogen.
Radioimmunoassay was used for hormone determination while serum proteins were determined with electroimmunoassay or in some studies for sex hormone binding globulin (SHBG) with capacity assays. Serum lipids and lipoproteins were determined in serum and after ultracentrifugation in HDL, LDL and VLDL fractions.
In a comparative study on levonorgestrel/ethinylestradiol (EE) (n = 10) versus desogestrel/ethinylestradiol (n=10) the latter combination gave increases in SHBG capacity while the former did not. Similar increases in estrogen-sensitive proteins Cortisol binding globulin (CBG) and ceruloplasmin indicated that the estrogenicity and “antiestrogenicity” was the same for the two combinations whereas the androgenicity of levonorgestrel was greater giving a reduction in the EE-induced increase in SHBG (SHBG is increased by estrogens and suppressed by androgens). When giving desogestrel 0.125–0.500 mg and lynestrenol 5 mg alone in daily doses to a group of regularly menstruating women (n = 8) strong suppression of SHBG was achieved while ceruloplasmin, CBG and thyroxine binding globulin (TBG) did not change. TBG is decreased and prealbumin increased by androgenic/anabolic activity but only a moderate increase in prealbumin was found during lynestrenol treatment. The changes in SHBG are probably the result of a dose-dependent receptor interaction related to 17a-alkylation in 19-norsteroids.
Twenty women with PCO were treated for 8 months with 0.150 mg desogestrel/0.030 mg EE. Evaluation was done before treatment and after 3 and 8 “pill” cycles regarding androgens, estradiol, SHBG, hirsutism and body weight. Spontaneous menstrual cycles were assessed after treatment. Serum lipids and lipoproteins were studied before treatment and at the end of the third “cycle”. In PCO the suppression of increased total and free testosterone levels (in comparison to 22 healthy women) was evident during treatment, concordant with increases in SHBG capacity. Hirsutism was suppressed and body weight was reduced in obese women. After treatment three women wishing pregnancy got pregnant and eight others continued menstruating. The other nine had a recurrence of PCO. The only difference in lipids before treatment in the PCO group compared to a group of healthy women (n = 13) were higher levels of triglycerides and VLDL triglycerides. During treatment only a higher VLDL triglyceride level was found in PCO women than in the normal control group. PCO women thus react in the same way as healthy women to desogestrel/EE treatment. No serious side effects were encountered and no significant changes in libido seen. It can be concluded that desogestrel is a strong progestogen lacking measurable androgenicity. It is a suitable progestogen for use in women with low SHBG capacity who are at risk for androgenic side effects.