Testosterone treatment prevents most gonadectomy-induced metabolic and skeletal deficiencies in female mice
7 affiliations
- 1Department of Obstetrics and Gynecology, University of Michigan
- 2Department of Pediatrics, University of Michigan
- 3Department of Biomedical Engineering, University of Michigan
- 4Department of Orthopaedic Surgery, University of Michigan
- 5Department of Internal Medicine, Division of Cardiovascular Medicine, University of Michigan
- 6Department of Molecular & Integrative Physiology, University of Michigan
- 7Reproductive Medicine Associates of Michigan
Abstract
Ovarian hormone depletion, whether due to ovariectomy, primary ovarian insufficiency, menopause, or gonadotoxic therapies, is associated with metabolic and skeletal dysfunction, while hyperandrogenic states such as polyendocrine metabolic ovarian syndrome are also linked to increased cardiometabolic risk. However, whether testosterone exacerbates, mitigates, or modifies the consequences of ovarian hormone loss remains poorly understood. This study examined whether testosterone treatment ameliorates ovariectomy-induced metabolic and skeletal impairments using an adult female mouse model. Eight-week-old CD-1 mice underwent sham surgery or ovariectomy and were implanted subcutaneously with capsules containing 10 mg testosterone or empty control capsules, yielding four experimental groups: Blank+Intact (n=7), Blank+OVX (n=7), Testosterone+Intact (n=7), and Testosterone+OVX (n=8). Each treatment combination resulted in hormonal milieus distinct to each group. After six weeks of treatment, testosterone mitigated ovariectomy-induced hyperglycemia and impaired glucose tolerance but did not prevent dyslipidemia or adipocyte hypertrophy (two-way ANOVA with Tukey’s post hoc test, p<0.05). Testosterone treatment also increased circulating triglycerides, heart weight, femoral trabecular bone density, and radial strength independent of ovarian status. These findings indicate that testosterone compensates for some, but not all, metabolic and skeletal consequences of ovarian hormone loss, revealing distinct roles for androgens and estrogens in metabolic homeostasis. This may inform clinical management of ovarian insufficiency, menopause, hyperandrogenic disorders, and testosterone-based therapies.
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BibTeX
@article{kruger2026testosterone,
title = {{Testosterone treatment prevents most gonadectomy-induced metabolic and skeletal deficiencies in female mice}},
author = {Robin E. Kruger and Hannah Yohannes and Evelyn Cho and Lainie Eisner and Daniel R. Pfau and Ruth K. Chan-Sui and Nicole Migotsky and Andre Monteiro da Rocha and Megan L. Killian and Molly B. Moravek and Vasantha Padmanabhan and Ariella Shikanov},
journal = {Frontiers in Endocrinology},
year = {2026},
month = oct,
doi = {10.3389/fendo.2026.1940100},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1940100/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Testosterone treatment prevents most gonadectomy-induced metabolic and skeletal deficiencies in female mice
AU - Robin E. Kruger
AU - Hannah Yohannes
AU - Evelyn Cho
AU - Lainie Eisner
AU - Daniel R. Pfau
AU - Ruth K. Chan-Sui
AU - Nicole Migotsky
AU - Andre Monteiro da Rocha
AU - Megan L. Killian
AU - Molly B. Moravek
AU - Vasantha Padmanabhan
AU - Ariella Shikanov
PY - 2026
DA - 2026/10/16
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1940100
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1940100/full
AB - Ovarian hormone depletion, whether due to ovariectomy, primary ovarian insufficiency, menopause, or gonadotoxic therapies, is associated with metabolic and skeletal dysfunction, while hyperandrogenic states such as polyendocrine metabolic ovarian syndrome are also linked to increased cardiometabolic risk. However, whether testosterone exacerbates, mitigates, or modifies the consequences of ovarian hormone loss remains poorly understood. This study examined whether testosterone treatment ameliorates ovariectomy-induced metabolic and skeletal impairments using an adult female mouse model. Eight-week-old CD-1 mice underwent sham surgery or ovariectomy and were implanted subcutaneously with capsules containing 10 mg testosterone or empty control capsules, yielding four experimental groups: Blank+Intact (n=7), Blank+OVX (n=7), Testosterone+Intact (n=7), and Testosterone+OVX (n=8). Each treatment combination resulted in hormonal milieus distinct to each group. After six weeks of treatment, testosterone mitigated ovariectomy-induced hyperglycemia and impaired glucose tolerance but did not prevent dyslipidemia or adipocyte hypertrophy (two-way ANOVA with Tukey’s post hoc test, p<0.05). Testosterone treatment also increased circulating triglycerides, heart weight, femoral trabecular bone density, and radial strength independent of ovarian status. These findings indicate that testosterone compensates for some, but not all, metabolic and skeletal consequences of ovarian hormone loss, revealing distinct roles for androgens and estrogens in metabolic homeostasis. This may inform clinical management of ovarian insufficiency, menopause, hyperandrogenic disorders, and testosterone-based therapies.
SN - 1664-2392
ER -