Modulation of Immunoradiometric and Bioactive Follicle Stimulating Hormone Secretion and Clearance in Young and Elderly Men During Treatment with Tamoxifen or Flutamide
Authors: URBAN RANDALL J. , DAHL KRISTINE D. , LIPPERT MARGUERITE C. , VELDHUIS JOHANNES D. 
Published: September 2023

ABSTRACT: The secretion and clearance of immunoactive and bioactive follicle‐stimulating hormone (FSH) in healthy young men (N = 10) and elderly men (N = 7) during blockade of endogenous sex steroid hormones with tamoxifen, an antiestrogen, and flutamide, an antiandrogen, was investigated. To this end, subjects underwent blood sampling basally every 10 minutes for 24 hours, and then received 2 consecutive intravenous pulses of synthetic gonadotropin releasing hormone (GnRH; 10 μg and 100 μg) every 2 hours. This paradigm was repeated on two subsequent visits, in which subjects received either flutamide HCl, a specific nonsteroidal competitive antagonist of the androgen receptor (750 mg daily for 3 days), or tamoxifen, a selective antagonist of the estrogen receptor (20 mg daily for 9 days). Serum immunoactive FSH concentrations were measured in each sample by immunoradiometric assay (IRMA). Serum bioactive FSH concentrations were determined by an in vitro bioassay (rat granulosa cell aromatase system) on 24‐hour serum pools. Deconvolution analysis was used to analyze both the FSH IRMA 24‐hour time series and FSH release after GnRH. Comparisons between young and elderly men of the basal state showed significantly increased 24‐hour mean serum immunoactive and bioactive FSH concentrations and significantly decreased free testosterone concentrations in elderly men. By deconvolution analysis, elderly men had a significant decrease in FSH secretory burst duration, and an increase in FSH half‐life and FSH secretory burst amplitude compared with younger men. In response to sex steroid receptor blockade in young men, there was a significant increase in mean serum bioactive FSH concentrations during antiandrogen treatment, but not during anti‐estrogen treatment. In contrast, in elderly men mean serum bioactive FSH concentrations decreased during flutamide and tamoxifen treatment. Young men showed a significant increase in FSH half‐life and serum concentrations of free testosterone and estradiol in response to flutamide and tamoxifen treatment. Mean FSH interburst interval, secretory burst duration, amplitude, and mass, and daily FSH production rates were unchanged during steroid receptor blockade. On the other hand, there was no change in mean serum FSH concentration or any parameter of FSH secretion or clearance in elderly men during treatment with flutamide or tamoxifen, but there was a significant increase in serum free testosterone (but not estradiol) concentrations. It is concluded that: (1) specific features of basal FSH secretion and clearance differ in young and elderly men; and (2) young and elderly men respond differently to treatment with antiestrogen or antiandrogen, implying altered responses to sex steroid negative feedback action with aging. The basis for such selective age‐dependent differences in the regulation of the FSH component of the reproductive axis in aging men is not known.