Assessment of pituitary gonadotropin release to gonadotropin releasing hormone/thyroid-stimulating hormone stimulation in women with systemic sclerosis

OBJECTIVE: To evaluate basal and dynamic levels of pituitary gonadotropin release in female systemic sclerosis (SSc) patients of childbearing age and in post-menopausal SSc patients. METHODS: We performed stimulation tests for gonadotropin-releasing hormone (GnRH) and thyroid-stimulating hormone (TRH) during the early follicular phase in 12 women of childbearing age [mean age (S.E.M.) 34.8 (2.4) yr] with SSc to determine serum concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and prolactin. Blood samples were also obtained from six post-menopausal women with SSc [mean age 46.8 (2.4) yr], after TRH stimulation; only serum prolactin concentration was determined, because elevated basal concentrations of FSH and LH were expected. Hormone concentrations were estimated by radioimmunoassay. Comparisons were made with healthy control women matched for age and reproductive status. RESULTS: In SSc patients of childbearing age, basal FSH, LH and oestradiol (E(2)) levels were not significantly different from those in controls, whereas basal prolactin concentration was significantly higher than in controls (P=0.0001). After the stimulation test, the peak concentrations of FSH (P=0.0001) and prolactin (P<0.0001) were significantly higher than in controls. The net integrated response curves [net area under the curve (AUC)] for FSH and LH did not differ significantly between SSc patients and controls. On the contrary, the net AUC for prolactin in response to TRH stimulation was significantly higher than in controls (P=0.001). In post-menopausal patients, basal E(2), FSH, LH and prolactin levels were not significantly different between women with SSc and controls. However, after TRH stimulation, peak levels and net AUC for prolactin were not significantly higher in patients than those in controls. No significant correlations were found between basal and stimulated FSH, LH and prolactin levels and the severity of involvement of various organ systems. Multiple regression analysis showed that basal and stimulated prolactin concentrations were associated with skin sclerosis and peripheral vascular and lung involvement. CONCLUSION: Our results suggest that subclinical primary hypogonadism can occur in SSc patients. They also confirm an alteration in the mechanism for prolactin secretion and release, which may not only contribute to further disturbance of the reproductive axis but may also have an influence on the disease.