Trial reportThe Journal of clinical investigation2016
Gonadal steroid-dependent effects on bone turnover and bone mineral density in men.
Trial report in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00114114 (Dose-Response of Gonadal Steroids and Bone Turnover in Older Men), which is not on this map. Cited by 80 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Dose-Response of Gonadal Steroids and Bone Turnover in Older Men
Who cites it
80 citing papers in PubMed, 4 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- Cardiovascular safety in middle-aged and older men under testosterone replacement therapy: a systematic review and meta-analysis.Endocrine · 2026Pooled it
- Incomplete Evidence of Bone Density Normalization Following Long-Term Reproductive Hormone Treatment in Men With Hypogonadotropic Hypogonadism.The Journal of clinical endocrinology and metabolism · 2025Pooled it
- Testosterone supplementation and bone parameters: a systematic review and meta-analysis study.Journal of endocrinological investigation · 2022Pooled it
- Gonadal Hormones in the Pathogenesis and Treatment of Bone Health in Patients with Chronic Kidney Disease: a Systematic Review and Meta-Analysis.Current osteoporosis reports · 2018Pooled it
- Sex Steroids Regulate Liver Fat Content and Body Fat Distribution in Both Men and Women: A Study in Transgender Persons.The Journal of clinical endocrinology and metabolism · 2023Trial
- Dimethandrolone Undecanoate, a Novel, Nonaromatizable Androgen, Increases P1NP in Healthy Men Over 28 Days.The Journal of clinical endocrinology and metabolism · 2021Trial
- Dose-Response Relationships Between Gonadal Steroids and Bone, Body Composition, and Sexual Function in Aging Men.The Journal of clinical endocrinology and metabolism · 2020Trial
- Daily Oral Administration of the Novel Androgen 11β-MNTDC Markedly Suppresses Serum Gonadotropins in Healthy Men.The Journal of clinical endocrinology and metabolism · 2020Trial
- Gender-Affirming Hormone Treatment Decreases Bone Turnover in Transwomen and Older Transmen.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- Bone and body composition response to testosterone therapy vary according to polymorphisms in the CYP19A1 gene.Endocrine · 2019Trial
- Effect of Testosterone on Natriuretic Peptide Levels.Journal of the American College of Cardiology · 2019Trial
- Safety and Pharmacokinetics of Single-Dose Novel Oral Androgen 11β-Methyl-19-Nortestosterone-17β-Dodecylcarbonate in Men.The Journal of clinical endocrinology and metabolism · 2019Trial
- AdipocytesNutrients · 2018Trial
- Effect of Testosterone Treatment on Volumetric Bone Density and Strength in Older Men With Low Testosterone: A Controlled Clinical Trial.JAMA internal medicine · 2017Trial
- Effects of Testosterone and Estradiol Deficiency on Vasomotor Symptoms in Hypogonadal Men.The Journal of clinical endocrinology and metabolism · 2016Trial
- A novel model to study the impact of gender-affirming therapy on bone in young male mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2026Article
- Bone-related adverse events of hormonal therapy: A pharmacovigilance study based on the Food & Drug Administration Adverse Event Reporting System.The Journal of international medical research · 2026Article
- Review
- Testosterone and Bone Health in Men.Current osteoporosis reports · 2026Review
- The orally available SIK2/SIK3 inhibitor SK-124 increases bone mass in hypogonadal male mice.JBMR plus · 2026Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
backgroundSevere gonadal steroid deficiency induces bone loss in adult men; however, the specific roles of androgen and estrogen deficiency in hypogonadal bone loss are unclear. Additionally, the threshold levels of testosterone and estradiol that initiate bone loss are uncertain.
methodsOne hundred ninety-eight healthy men, ages 20-50, received goserelin acetate, which suppresses endogenous gonadal steroid production, and were randomized to treatment with 0, 1.25, 2.5, 5, or 10 grams of testosterone gel daily for 16 weeks. An additional cohort of 202 men was randomized to receive these treatments plus anastrozole, which suppresses conversion of androgens to estrogens. Thirty-seven men served as controls and received placebos for goserelin and testosterone. Changes in bone turnover markers, bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA), and BMD by quantitative computed tomography (QCT) were assessed in all men. Bone microarchitecture was assessed in 100 men.
resultsAs testosterone dosage decreased, the percent change in C-telopeptide increased. These increases were considerably greater when aromatization of testosterone to estradiol was also suppressed, suggesting effects of both testosterone and estradiol deficiency. Decreases in DXA BMD were observed when aromatization was suppressed but were modest in most groups. QCT spine BMD fell substantially in all testosterone-dose groups in which aromatization was also suppressed, and this decline was independent of testosterone dose. Estradiol deficiency disrupted cortical microarchitecture at peripheral sites. Estradiol levels above 10 pg/ml and testosterone levels above 200 ng/dl were generally sufficient to prevent increases in bone resorption and decreases in BMD in men.
conclusionsEstrogens primarily regulate bone homeostasis in adult men, and testosterone and estradiol levels must decline substantially to impact the skeleton.
trial registrationClinicalTrials.gov, NCT00114114.
fundingAbbVie Inc., AstraZeneca Pharmaceuticals LP, NIH.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.