Effects of Testosterone and Estradiol Deficiency on Vasomotor Symptoms in Hypogonadal Men

J Clin Endocrinol Metab. 2016 Sep;101(9):3479-86. doi: 10.1210/jc.2016-1612. Epub 2016 Jun 14.

Abstract

Context: The hormonal basis of vasomotor symptoms (VMS) in hypogonadal men is incompletely understood.

Objective: To determine the contributions of testosterone and estradiol deficiency to VMS in hypogonadal men.

Design: Two randomized trials were conducted sequentially between September 2004 and April 2011. Controls were recruited separately.

Setting: A single-site academic medical center.

Participants: Healthy men ages 20-50, with normal serum testosterone levels.

Intervention: Cohort 1 (n = 198, 81% completion) received goserelin acetate every 4 weeks to suppress gonadal steroids and were randomized to placebo or 1.25, 2.5, 5, or 10 g of testosterone gel daily for 16 weeks. Cohort 2 (n = 202, 78% completion) received the same regimen as cohort 1 plus anastrozole to block aromatization of testosterone. Controls (n = 37, 89% completion) received placebos for goserelin acetate and testosterone.

Main outcome measures: Incidence of visits with VMS. This was a preplanned secondary analysis.

Results: VMS were reported at 26% of visits in cohort 1, and 35% of visits in cohort 2 (P = .02), demonstrating an effect of estradiol deficiency. When adjacent estradiol level groups in cohort 1 were compared, the largest difference in VMS incidence was observed between the 5-9.9 and 10-14.9 pg/mL groups (38% vs 16%, P < .001). In cohort 2, the 10-g testosterone group differed significantly from placebo (16% vs 43%, P = .048) after adjustment for small differences in estradiol levels, indicating that high testosterone levels may suppress VMS.

Conclusions: Estradiol deficiency is the key mediator of VMS in hypogonadal men. At high levels, testosterone may have a suppressive effect.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Biomarkers / analysis
  • Blood Glucose / analysis
  • Case-Control Studies
  • Diabetes Mellitus, Type 1
  • Diabetes Mellitus, Type 2
  • Estradiol
  • Female
  • Follow-Up Studies
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Hypogonadism
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Testosterone

Substances

  • Biomarkers
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Testosterone
  • Estradiol