The Thyrotropin (TSH) Profile in Isolated Gonadotropin Deficiency: A Model to Evaluate the Effect of Sex Steroids on TSH Secretion*

Abstract

This study evaluated the effect of estrogens and androgens on TSH secretion in hypogonadal male and female patients with isolated gonadotropin deficiency (IGD). The IGD subjects were clinically euthyroid and had normal circulating levels of thyroid hormones and T4-binding globulin (TBG). The patients were challenged with TRH (200 micrograms) in the untreated state, during treatment, and 1 month after cessation of hormonal replacement therapy. For the study, five females were treated with ethinyl estradiol (0.05 mg twice daily) for 21 days; after stopping for 7 days, the treatment schedule was repeated for another two cycles. The remaining female was given a similar regimen with conjugated estrogens (0.625 mg daily). Five males were treated with hCG (5000 IU twice weekly) for 3 months; two were treated with hCG and Pergonal. The female patients had significantly decreased basal TSH levels as well as impaired TSH responses to TRH. After 3 months of ethinyl estradiol treatment, there was a rise in TBG, total serum T4 and T3 levels and a decrease in T3 resin uptake; the free T4 index was unchanged. During estrogen administration, there was no change in basal TSH, but there was an increase in the peak TSH response to TRH, which became identical to that of the controls. Cessation of estrogen was associated with a reduction in releasable TSH, and the profile reverted to the pretreatment state. In addition, serum TBG levels, with the associated changes in thyroid hormones, also returned to normal. The male patients had TSH responses to TRH identical to those of the male controls. After 3 months of hCG treatment, there was a marked rise in serum estradiol as well as testosterone. Serum T4 was reduced without a change in T3, T3 resin uptake, or TBG. Furthermore, there was no alteration in the TSH response to TRH. On the other hand, the administration of ethinyl estradiol (0.1 mg daily for 2 weeks) to two male IGD subjects produced an increase in TBG. This was associated with elevation of serum T4 and T3 levels and reduction of T3 resin uptake. During estradiol administration, there was an increase in the TSH response to TRH. These data are compatible with the hypothesis that estrogens are required to maintain a normal TSH response to TRH in the female. However, testosterone may counteract the effect of estradiol, which may explain why normal males tend to have a lower TSH response to TRH than females.

Chronic Treatment with Low Doses of Estradiol Affects Pituitary and Thyroid Function in Young and Middle-aged Ovariectomized Rats

“…Another report describing the effect of daily injections with 2 lg E2B in ovariectomized rats also reported an elevation of TSH levels (Chen and Walfish 1978). In contrast, our results are confirmed by several human studies that did not detect alterations in TSH serum levels in women taking oral contraceptives (Spitz et al 1983;Kuhl et al 1985;Toldy et al 2004).…”

Modulation by oestrogen of thyroid hormone effects on thyrotrophin gene expression

“…In man, administration of oestrogen is reported to have no effect on basal serum concentrations of TSH (Rutlin, Haug & Torjesen, 1977;Spitz, Zylber-Haran & Trestian, 1983;Abdalla, Hart & Beastall, 1984), but thyrotrophin-releasing hormone (TRH)-stimulated release may be augmented or unchanged (Woolf, González-Barcena, Schalch et al 1973;Mortimer, Besser, Goldie et al 1974;Spitz et al 1983). In the euthyroid rat, treatment with oestrogen has no effect on basal serum TSH or TRH-stimulated release of TSH (Boado, Ulloa & Zaninovich, 1983;Boado, Deza & Zaninovich, 1985), but in the ovariectomized animal, oestrogen replacement has been reported to increase basal TSH concentration and enhance the TSH response to TRH (Chen & Walfish, 1978).…”

Should human chorionic gonadotropine treatment increase thyroid volume?

“…Androgen replacement treatment (testosterone or gonadotropin treatment) have been used to in these patients (2). There was limited data about the effects of sex hormones and hCG on thyroid functions and thyroid volume among hypogonadal male patients (14,(16)(17)(18). Spitz and cols.…”

“…Spitz and cols. (16), evaluated the effect of estrogens and androgens on TSH secretion in hypogonadal male and female patients. Male patients showed a transient reduction in serum T4 during hCG therapy.…”