Research · PMID 11730247
Reviewed by Neal Rouzier, MD, Preventive Medicine · Sep 2026
Estrogens and bone health in men.
Calcified tissue international · October 2001 · S Khosla, L J Melton, B L Riggs
What this study found
It has generally been held that estrogen and testosterone are the major sex steroids regulating bone metabolism in women and men, respectively. However, the description of several "experiments of nature" led to a reconsideration of this notion.
How RAGMD uses this study
Clinical questions this paper informs
Synthesis lives on the evidence question — this page shows where the study sits in that analysis.
Core study
Does estradiol level affect symptoms and bone health in men on testosterone therapy?
Estradiol in men derives largely from aromatization of testosterone and contributes to bone density and possibly symptom control. Over-suppression with aromatase inhibitors may impair bone health; optimal targets in clinical practice remain debated.
Open evidence analysisSupporting literature
Does testosterone therapy increase prostate cancer risk?
Current systematic reviews and trial secondary analyses do not show a convincing increase in prostate cancer incidence among hypogonadal men treated with testosterone, though surveillance remains standard practice.
Open evidence analysisSupporting literature
Does testosterone therapy increase hematocrit and polycythemia risk?
Testosterone therapy commonly raises hematocrit; polycythemia is a recognized adverse effect requiring dose adjustment, formulation changes, or phlebotomy when thresholds are exceeded.
Open evidence analysisSupporting literature
Does testosterone therapy suppress fertility in men?
Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and reliably reduces spermatogenesis. Recovery after discontinuation is variable and may be incomplete in some men.
Open evidence analysisSupporting literature
Does testosterone therapy increase venous thromboembolism risk?
Large observational cohorts suggest a modest increase in venous thromboembolism risk with testosterone therapy, particularly early after initiation. Absolute risk remains low in most populations but warrants attention in predisposed patients.
Open evidence analysisSupporting literature
Do aromatase inhibitors in men increase bone loss risk?
Aromatase inhibitors lower estradiol and can reduce bone mineral density in men. Routine use to suppress estradiol during testosterone therapy is not supported by outcome evidence and may carry skeletal risk.
Open evidence analysisSupporting literature
Does testosterone therapy worsen obstructive sleep apnea?
Testosterone may worsen sleep apnea in predisposed men. Screening and monitoring for OSA is recommended before and during therapy, especially when symptoms emerge or hematocrit rises.
Open evidence analysisSupporting literature
Does testosterone therapy improve depression or low mood in hypogonadal men?
Some randomized trials and meta-analyses show modest improvements in depressive symptoms among men with low testosterone, but effects are heterogeneous and not a substitute for standard psychiatric evaluation when major depression is present.
Open evidence analysisSupporting literature
How should low testosterone be diagnosed in symptomatic men?
Diagnosis requires consistent symptoms plus repeatedly low morning total testosterone on valid assays, with secondary causes excluded. A single borderline value should prompt repeat testing before initiating therapy.
Open evidence analysisSupporting literature
Do transdermal and injectable testosterone differ in safety or efficacy?
All FDA-approved formulations can restore testosterone when dosed appropriately. Transdermal routes may have less erythrocytosis than injectable esters in some comparisons, but transfer, adherence, and peak-trough patterns differ by formulation.
Open evidence analysis