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Updated: Jul 11, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Of mice and men: the many guises of estrogens
1Prince Henry's Institute of Medical Research, P.O. Box 5152, VIC 3168 Clayton, Australia. evan.simpson@princehenrys.org
Abstract:
Models of estrogen insufficiency have revealed new and unexpected roles for estrogens in males as well as females. These models include natural mutations in the aromatase gene in humans, as well as mouse knock-outs of aromatase and the estrogen receptors, and one man with a mutation in the ERa gene. These mutations, both natural and experimental, have revealed that estrogen deficiency results in a spectrum of symptoms. These include loss of fertility and libido in both males and females; loss of bone in both males and females; a cardiovascular and cerebrovascular phenotype; development of a metabolic syndrome in both males and females, with truncal adiposity and male-specific hepatic steatosis. Most of these symptoms can be reversed or attenuated by estradiol therapy. Thus estrogen is involved in the maintenance of general physiological homeostasis in both sexes.
Insights
Estrogen is vital for overall health in both males and females, impacting fertility, bone density, and metabolism. Estrogen insufficiency causes various health issues, but therapy can reverse many symptoms.
Area of Science:
- Endocrinology
- Reproductive Biology
- Metabolic Health
Background:
- Estrogens play crucial roles beyond reproduction, influencing physiological homeostasis in both sexes.
- Understanding estrogen's functions requires studying conditions of estrogen insufficiency.
- Previous research hinted at broader roles, but comprehensive effects remained unclear.
Purpose of the Study:
- To investigate the diverse physiological consequences of estrogen insufficiency in males and females.
- To identify specific symptoms associated with estrogen deficiency across various organ systems.
- To evaluate the therapeutic potential of estradiol in reversing estrogen deficiency-related phenotypes.
Main Methods:
- Analysis of human genetic mutations affecting aromatase and estrogen receptors (ERα).
- Utilizing mouse models with targeted knock-outs of aromatase and estrogen receptors.
- Observational studies on individuals with natural mutations impacting estrogen signaling.
Main Results:
- Estrogen deficiency leads to reduced fertility and libido in both sexes.
- Bone loss (osteoporosis) and cardiovascular/cerebrovascular issues are observed in both males and females.
- Metabolic syndrome, including central obesity and male-specific fatty liver disease, develops.
- Most observed symptoms are reversible or improved with estradiol administration.
Conclusions:
- Estrogen is essential for maintaining physiological homeostasis in both males and females.
- Estrogen insufficiency results in a wide spectrum of detrimental health effects.
- Estradiol therapy offers a viable strategy for mitigating the adverse consequences of estrogen deficiency.
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