Related Experiment Video
Updated: Apr 5, 2026

An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Hormone therapy in menopause: An update on cardiovascular disease considerations
Georgina E Hale1, Chrisandra L Shufelt2
1University of Sydney, Camperdown, New South Wales, Australia.
Insights
Menopausal hormone therapy (MHT) may prevent cardiovascular disease (CVD) if started early, but risks and benefits require more research. MHT is suitable for managing menopausal symptoms in younger women without apparent CVD risk.
Area of Science:
- Cardiology
- Endocrinology
- Women's Health
Background:
- Cardiovascular disease (CVD) is a leading global cause of death.
- Coronary risk factors are increasing in women, despite declining overall CVD incidence.
- Menopausal hormone therapy (MHT) has a complex history regarding CVD prevention.
Purpose of the Study:
- To evaluate the role of MHT in primary CVD prevention.
- To examine the impact of MHT timing, route, and dosage on CVD risk.
- To clarify the benefits versus risks of MHT for cardiovascular health.
Main Methods:
- Analysis of observational and interventional study data, including the Women's Health Initiative (WHI).
- Focus on the 'timing hypothesis' for MHT initiation (within 10 years of menopause, <60 years old).
- Comparison of different MHT formulations (transdermal estradiol, oral estradiol, CEE) and dosages.
Main Results:
- Early MHT initiation (timing hypothesis) may offer primary CVD prevention benefits.
- Transdermal estradiol may be safer for CVD risk than conventional CEE.
- Oral estradiol may reduce stroke risk compared to conventional CEE.
- Low-dose CEE might be beneficial for certain CVD events.
- Lower estrogen doses and transdermal routes may mitigate some CVD risks.
Conclusions:
- MHT is not currently recommended for CVD prevention due to unresolved benefit-risk questions.
- MHT is indicated for menopausal symptom management in eligible women (<60 years, within 10 years of menopause) without apparent increased CVD risk.
- Further research is essential to confirm the comparative safety of various MHT options for cardiovascular outcomes.
Abstract:
Cardiovascular disease (CVD) remains the number one cause of death and morbidity worldwide, and while overall CVD incidence rates declined in both genders between 1999 and 2007, age-specific data suggest that coronary risk factors in women are on the rise. While early observational data favored menopausal hormone therapy's (MHT's) role in primary CVD prevention, the initial interventional study data from the WHI did not. Further detailed analyses of both observational and interventional data have pointed to the possibility that MHT may play a role in primary CVD prevention if initiated within 10 years of menopause and less than 60 years of age (the timing hypothesis). Unanswered questions remain regarding the optimal route and dosage of estrogen in MHT. Data so far, favor transdermal estradiol over conventional-dose CEE with respect to CVD risk and oral estradiol over conventional-dose CEE with respect to stroke risk. Low-dose oral CEE may similarly have benefit over conventional-dose oral CEE for some CVD events. In addition, the transdermal route of delivery may avoid the excess risk of certain CVD events associated with MHT and lower doses of estrogen may have fewer adverse effects than the doses previously tested in WHI. Because questions regarding benefits versus risks remain, MHT is yet to be recommended for CVD prevention. However, it is indicated for menopausal symptom management in women within 10 years of menopause and under the age of 60 years, in whom it does not appear to carry increased cardiovascular risk. Additional research is ongoing and needed to confirm or refute the comparative safety of the various MHT options.
Related Concept Videos
Menopause
Hormonal Regulation of the Menstrual Cycle
At puberty, GnRH begins a pulsatile release pattern, which triggers the anterior pituitary gland to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The frequency and amplitude of GnRH pulses vary across the menstrual cycle, with faster pulses favoring LH release and slower pulses favoring FSH...
Hormonal Regulation of Blood Pressure
Epinephrine and Norepinephrine
The adrenal medulla releases epinephrine and norepinephrine, catecholamines that enhance and extend the sympathetic or "fight or flight" physiological response. These hormones escalate heart rate and the force of contraction...
Atherosclerosis III: Management
Psychoneuroimmunology: Cardiovascular Disease
A key area of focus in PNI is the relationship between stress and coronary...
Hormonal Control of the Ovarian Cycle
Before puberty, the hypothalamus releases GnRH in a low frequency, low amplitude pulsatile manner. This along with the immature hypothalamic-pituitary-gonadal axis activity, results in low estrogen levels and the absence of a fully functional ovarian cycle. At puberty, GnRH secretion increases in both frequency and...

