Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism

Background: While the effects of thyroxine (T4) replacement on improving gonadal function in hypothyroid men has been well documented, the same has not been adequately studied in hypothyroid premenopausal women. Methodology: Premenopausal women with overt hypothyroidism (thyroid-stimulating hormone [TSH] > 15 IU/L) were tested in the early follicular phase of their natural menstrual cycles or after a progesterone challenge for gonadotropins, estradiol (E2), and prolactin (PRL). They were then treated adequately with T4 replacement and retested under similar circumstances for the same parameters 2 months after the restoration of euthyroidism. Results: Forty premenopausal hypothyroid women were evaluated at baseline and 2 months after adequate T4 replacement. At baseline, there was an inverse correlation of the gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and TSH, prolactin (PRL) and free T4 (fT4), and E2 and PRL. After normalization of the thyroid function, there was a significant fall in PRL (p < 0.001) accompanied by a rise in serum E2 (p < 0.001). There were no changes in the levels of the gonadotropins LH and FSH. The proportion of patients with hyperprolactinemia fell 5-fold, from 5/40 to 1/40. While there were 5 patients with low estrogen prior to treatment, there were none with hypoestrogenemia after treatment. Conclusion: Hypothyroidism is associated with a reversible partial suppression of the hypothalamo-pituitary-gonadal axis in premenopausal women, demonstrated by lower E2 along with a mild elevation of PRL. Treatment of hypothyroidism improves the level of estrogen and lowers the level of PRL.