Reduced androgen levels in adult turner syndrome: influence of female sex steroids and growth hormone status.

BACKGROUND AND OBJECTIVES: In girls with Turner syndrome androgen levels are reduced. In order to assess androgen status in women with Turner syndrome, we compared untreated adult women with Turner syndrome with a group of normal women. In addition, the effects of female sex hormone replacement therapy and GH status on the levels of circulating androgens in Turner syndrome was examined.
DESIGN: All patients were receiving female hormone replacement therapy (HRT), which was discontinued four months prior to the initial examination. Patients were studied before and during HRT. Following the initial evaluation, patients were given cyclical HRT for six months consisting of either oral substitution (17beta-oestradiol with norethisterone from day 13-22), or transdermal oestrogen substitution (17beta-oestradiol) with 1 mg norethisterone administered orally from day 13-22. Control subjects were studied once in the early follicular stage of the menstrual cycle.
SUBJECTS: The study group consisted of 27 (33.2 +/- 7.9 years) patients with Turner syndrome and an age matched control group of 24 (32.7 +/- 7.6 years) normal women. MEASUREMENTS: Body composition measures, SHBG, testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), alpha-4-androstendione (A), dehydroepiandrosterone sulphate (DHEAS), 17beta-oestradiol (E2), oestrone (E1), oestrone sulphate (ES), 24 h integrated GH concentration (ICGH), insulin-like growth factor I (IGF-I), insulin-like growth factor binding protein (IGFBP-3) were determined at baseline and after six months in women with Turner syndrome, and at baseline in control women.
RESULTS: Circulating levels of A, T, FT, DHT, and SHBG were reduced by 25-40% in comparison with age matched normal women. The level of DHEAS was normal. The level of E2 was undetectable and levels of E1 and ES were very low in untreated Turner women. Treatment with 17beta-oestradiol and norethisterone increased oestrogen to levels comparable to those of normal women, while further decreasing FT (P = 0.02), DHT (P = 0.04), and T (P = 0.1). In untreated women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.503, P < 0.01), while in normal women IGF-I correlated with A (R = 0.637, P < 0.01), T (R = 0.536, P < 0.01), and FT (R = 0.700, P < 0.01). During hormonal replacement in women with Turner syndrome IGF-I correlated significantly with DHEAS (R = 0.547, P < 0.01). Employing multiple regression analysis IGFBP-3, ICGH, DHEAS and fat free mass explained 85% (adjusted R = 0.92, P < 0.0005) of the variation in the level of IGF-I in untreated Turner syndrome. In treated Turners IGFBP-3, ICGH, SHBG, T, and FT explained 78% (adjusted R = 0.88, P < 0.0005). In controls IGFBP-3, SHBG, BMI and age explained 74% (adjusted R = 0.86, P < 0.0005) of the variation in IGF-I, while GH status did not contribute at all.
CONCLUSION: The present study shows that many adults with Turner syndrome have reduced levels of circulating androgens, compared with an age-matched group of normal women. Conditions associated with Turner syndrome such as increased prevalence of sexual problems, reduced bone mineral content, osteoporosis, and an increased incidence of fractures and alterations in body composition could perhaps be alleviated or abolished by substitution with a low dose of androgens. Treatment with female hormonal replacement therapy is associated with a decrease in testosterone, free testosterone and dihydrotestosterone, possibly mediated by the androgenic effect of norethisterone. Furthermore significant differences in sex steroid levels, GH status and indices of body composition can be compatible with comparable levels of IGF-I in two very different groups of individuals.