The Androgen Status Of Young Women With Premature Ovarian Failure Depends On The Female Sex Steroid Replacement Regimen
A Mason1, M A Wallace2, H MacIntyre2, P Y Teoh2, L E Bath3, H O Critchley4, C J H Kelnar3, H W B Wallace3 & S F Ahmed1
Author affiliations
1Bone and Endocrine Research Group, RHSC Glasgow., Glasgow, UK; 2Department of Clinical Biochemistry, Glasgow Royal Infirmary, Glasgow, UK; 3Department of Child Health, RHSC Edinburgh, Edinburgh, UK; 4Deparment of Reproductive and Developmental Sciences, Centre for Reproductive Biology, University of Edinburgh, Edinburgh, UK.
Aims: To compare the effect of a standard Sex Steroid Regimen (sSSR) with a physiological SSR (pSSR) on androgen status in young women with premature ovarian failure (POF).
Patient Population: Seven women with POF were evaluated for the study. The median age was 28 years (range 21–36) and the median duration of ovarian failure was 14 years (range 4–25).
Methods: An open label randomised, controlled, crossover study over 28 months comparing the effect of sSSR and pSSR on androgen status. Treatment consisted of a 12 month period of 4-week cycles of pSSR (transdermal estradiol 100 mcg daily for week 1 and 150 mcg for weeks 2–4 and either 200 mg progesterone vaginal pessaries or progesterone 10 mg orally twice daily in weeks 3–4), or sSSR (Loestrin 30, Galen Ltd; ethinylestradiol 30 mcg and norethisterone 1.5 mg daily for weeks 1–3, followed by 7 pill-free days), separated by run-in and wash-out periods. Serum Testosterone (T), Androstenedione (A4), SHBG were measured and the Free Andogen Index (FAI={serum T/SHBG} × 100) calculated at months 0/6/12.
Results: At baseline in the sSSR group, median T, A4 and SHBG were not significantly different from those in the pSSR group. Median T at 6 and 12 months were 1.1 and 1 nmol/l (sSSR) and 1.6 and 1.8 nmol/l (pSSR). Median A4 at 6 and 12 months were 5.6 and 4.7 nmol/l (sSSR) and 5.5 and 6.4 nmol/l (pSSR). Median SHBG at 6 and 12 months were 105 and 110 nmol/l (sSSR) and 62 and 66 nmol/l (pSSR). Median SHBG was significantly higher in the sSSR group at 6 and 12 months (P<0.02). Median FAI fell in the sSSR group from 2.4(2.2;7.4) at 0 months to 0.7(0.5;3.1) at 12 months (P=0.02); this fall was not seen in the pSSR arm.
Conclusion: pSSR, not associated with any further decline in free androgen levels, is an attractive treatment for long-term replacement in young women with POF.