Administration of L-thyroxine does not improve the response of the hypothalamo-pituitary-ovarian axis to clomiphene citrate in functional hypothalamic amenorrhea

Abstract Objective: To investigate the hypothalamo–pituitary–ovarian axis in women with functional hypothalamic amenorrhea to determine whether the combination of l -thyroxine and clomiphene citrate produces a qualitative and quantitative increase in induced ovulatory cycles. Setting: Gynecological Endocrinology Research Center, University of Siena (Italy). Patients: 16 young women with functional hypothalamic amenorrhea and 15 women with normal cycles in early follicular phase. Design: Administration of 50 μg GnRH and 200 μg TRH. The women with functional hypothalamic amenorrhea were divided into groups A ( n =8) and B ( n =8). Both groups were given 100 mg/day clomiphene for 5 days/month for 3 months. Women in group A were also given 75 mcg/day thyroid hormone ( l -thyroxine) for 3 months. Main outcome measures: Comparison of basal and stimulated levels of gonadotropins, TSH and Prl, in groups A and B. Qualitative and quantitative comparison of ovulatory cycles induced in the groups. Results: Administration of clomiphene and clomiphene plus l -thyroxine was evaluated in the second and third months of treatment and was followed by a total of 11 ovulatory cycles, six in group A and five in group B. No significant difference was found between groups. Mean progesterone concentrations measured 16 days after the last clomiphene tablet were 5.5±1.2 ng/ml in group A and 5.1±1.3 ngl/ml in group B. Conclusions: Administration of l -thyroxine with clomiphene does not improve the response of the hypothalamo–pituitary–ovarian axis to clomiphene citrate or the number of ovulatory cycles and does not reduce luteal phase defects.