by Donna White – © Donna White BHRT Training Academy™ 2024
Hormone Replacement Therapy (HRT) has been the subject of extensive research and debate within the medical community. This article aims to present a detailed, evidence-based review of HRT’s safety and efficacy, addressing its use across different age groups and stages of menopause.
Timing of HRT Initiation
- Early Initiation:
○ The “timing hypothesis” suggests that starting HRT before age 60 or within 10 years of menopause is associated with reduced atherosclerosis progression, coronary heart disease, and cardiovascular mortality (Hamoda et al., 2020).
○ A systematic review by Nudy et al. (2019) found that younger menopausal women using HRT for vasomotor symptoms did not show an increased risk of coronary heart disease events or mortality. - Later Initiation:
○ Gu et al. (2024) reported that women starting MHT more than 10 years after menopause still showed improvements, although to a lesser degree than early initiators.
○ Importantly, no increase in cardiovascular events, cardiovascular mortality, or all-cause
mortality was observed in women who initiated HRT more than 10 years after menopause (Hamoda et al., 2020). - Longevity Benefits:
○ A study by Akter et al. (2022) found increased longevity in HRT users, including those who initiated therapy later in life.
○ Paganini-Hill et al. (2018) observed increased longevity in older users of postmenopausal
estrogen therapy in the Leisure World Cohort Study.
Cardiovascular Health
Overall Cardiovascular Risk:
○ A 2024 meta-analysis by Gu et al. found no increase in all-cause death or cardiovascular events with HRT use, despite an increased risk of stroke and venous thromboembolism. (Oral)
Transdermal vs. Oral Administration:
○ Transdermal estrogen does not increase the risk of venous thromboembolism (VTE), unlike some oral estrogens (Hamoda et al., 2020).
○ Women with obesity using estrogen-only or combined transdermal MHT did not show an increased risk of thrombotic events (Palacios et al., 2024).
Stroke Risk:
○ Oral estrogen may slightly increase stroke risk, particularly in women over 70.
○ Transdermal estrogen is unlikely to increase stroke risk as it does not alter thrombin function (Hamoda et al., 2020).
Heart Disease:
○ In women with acute coronary syndrome, HRT showed no significant difference in 90-day mortality, stroke, CVD event rate, and 1-year death rate compared to non-users (Parsons et al., 2004).
○ Some studies suggest a decreased risk of death and adverse events in hormone users post-coronary artery bypass grafting (Sullivan et al., 1997; Khan et al., 2000).
Cancer Risk
Breast Cancer:
○ The WHI follow-up study (Chlebowski et al., 2020) found that estrogen alone was associated with a 22% decrease in breast cancer incidence and a 40% decrease in breast cancer mortality.
○ Combined estrogen-progestogen therapy showed a 28% increase in breast cancer risk (Chlebowski et al., 2020). (Note: the progestogen was medroxyprogesterone acetate which is a synthetic progestin, not bioidentical progesterone.)
○ The E3N study (Fournier et al., 2008) found that progesterone did not increase breast cancer risk, while synthetic progestins slightly increased the risk.
○ Yuk et al. (2024) reported lower breast cancer mortality rates with MHT than without MHT.
Colorectal Cancer:
○ HRT has been associated with a significant decrease (up to 63%) in colorectal cancer risk in postmenopausal women (Rennert et al., 2009).
Ovarian Cancer:
○ Estrogen monotherapy beyond age 65 years was associated with a 13% reduction in ovarian cancer risk (Baik et al., 2024).
Bone Health
Osteoporosis Prevention:
○ HRT is considered a first-line treatment for osteoporosis prevention in women with premature ovarian insufficiency and menopausal women below 60 years of age (Hamoda et al., 2020).
○ Estrogen monotherapy beyond age 65 years was associated with a 15% reduction in fracture risk and a 7% reduction in osteoporosis risk (Baik et al., 2024).
Long-term Effects:
○ Combined estrogen-progestogen therapy showed a 10% reduction in fractures and a 9% reduction in osteoporosis risk (Baik et al., 2024).
Cognitive Function
Dementia Risk:
○ HRT is unlikely to increase the risk of dementia or negatively affect cognitive function when initiated before 60 (Hamoda et al., 2020).
○ Estrogen monotherapy beyond age 65 years was associated with a 2% reduction in dementia risk (Baik et al., 2024).
Cognitive Performance:
○ Some studies suggest that estrogen therapy may enhance cognitive outcomes post-menopause, particularly under specific dietary conditions (Hiroi et al., 2016).
Quality of Life
Vasomotor Symptoms:
○ Estrogen replacement remains the most effective treatment for vasomotor symptoms (Hamoda et al., 2020).
Musculoskeletal Symptoms:
○ Significant improvement in joint aches has been observed with HRT, showing a beneficial role in improving menopause-related musculoskeletal symptoms (Hamoda et al., 2020).
Sexual Function:
○ Testosterone has shown value in treating hypoactive sexual desire disorder (HSDD) in
postmenopausal women (Hamoda et al., 2020).
Personalized Approach and Monitoring
Individual Assessment:
○ Treatment should be tailored based on each patient’s unique hormonal profile, symptoms, health
status, and personal preferences.
○ Consider factors such as age, time since menopause, cardiovascular risk factors, and
personal/family history of hormone-sensitive cancers.
Regular Monitoring:
○ Implement protocols for ongoing assessment of hormone levels, symptoms, and potential side effects.
○ Adjust treatment as needed based on patient response and changing health status.
Choice of Hormone Formulation:
○ Consider transdermal estrogen and micronized progesterone for potentially safer profiles, especially in women at higher risk for thrombotic events.
Conclusion
The current body of evidence supports the safety and efficacy of BHRT across various age groups when appropriately prescribed and monitored. While earlier initiation may offer more pronounced benefits in some areas, women who start HRT later in life can still experience significant improvements in quality of life and overall health. The benefits often outweigh the risks for symptomatic menopausal women when therapy is tailored to individual needs and risk factors.
As with any medical intervention, the decision to use BHRT should be made individually, considering the patient’s overall health, risk factors, and preferences. This comprehensive, evidence-based approach allows medical providers to offer their patients effective symptom relief and potential long-term health benefits while minimizing risks, regardless of the age at which therapy is initiated.
References
- Akter, N., Kulinskaya, E., Steel, N., & Bakbergenuly, I. (2022). The effect of hormone
replacement therapy on the survival of UK women: a retrospective cohort study 1984-2017. BJOG: An
International Journal of Obstetrics and Gynaecology, 129(6), 994–1003. - Baik, S.A., et al. (2024). Use of Menopausal Hormone Therapy Beyond Age 65 Years and Its Effects
on Women’s Health Outcomes by Types, Routes, and Doses. JAMA, 332(1), 65-80. - Chlebowski, R.T., et al. (2020). Association of Menopausal Hormone Therapy With Breast Cancer
Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized
Clinical Trials. JAMA, 324(4), 369-380. - Fournier, A., et al. (2008). Unequal risks for breast cancer associated with different hormone
replacement therapies: results from the E3N cohort study. Breast Cancer Research and Treatment,
107(1), 103-111. - Gu, Y., et al. (2024). The benefits and risks of menopause hormone therapy for the
cardiovascular system in postmenopausal women: a systematic review and
meta-analysis. BMC Women’s Health, 24(1), 60. - Hamoda, H., et al. (2020). The British Menopause Society & Women’s Health Concern 2020
recommendations on hormone replacement therapy in menopausal women. Post Reproductive Health,
26(4), 181-209. - Hiroi, R., et al. (2016). Benefits of Hormone Therapy Estrogens Depend on Estrogen Type:
17β-Estradiol and Conjugated Equine Estrogens Have Differential Effects on Cognitive, Anxiety-Like,
and Depressive-Like Behaviors and Increase Tryptophan Hydroxylase-2 mRNA Levels in Dorsal Raphe
Nucleus Subregions. Frontiers in Neuroscience, 10, 517. - Khan, M.A., et al. (2000). Long-term (three years) effect of estrogen replacement therapy on
major adverse cardiac events in postmenopausal women after intracoronary stenting. American Journal
of Cardiology, 86(6), 330-333. - Manson, J.E., et al. (2024). Benefits of Lower-Dose and Non-Oral Hormone Replacement Therapy.
JAMA, 331(4), 357-369. - Nudy, M., et al. (2019). A systematic review and meta-regression analysis to examine the
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- Paganini-Hill, A., Corrada, M.M., & Kawas, C.H. (2018). Increased longevity in older users of
postmenopausal estrogen therapy: the Leisure World Cohort Study. Menopause, 25(11), 1256-1261. - Palacios, S., et al. (2024). Obesity and menopause. Gynecological Endocrinology, 40(1),
2312885. - Parsons, E., et al. (2004). Postmenopausal hormone use in women with acute coronary syndromes.
Journal of Women’s Health, 13(8), 863-871. - Rennert, G., et al. (2009). Use of hormone replacement therapy and the risk of colorectal
cancer. Journal of Clinical Oncology, 27(27), 4542-4547. - Sullivan, J.M., et al. (1997). Effect on survival of estrogen replacement therapy after
coronary artery bypass grafting. The American Journal of Cardiology, 79(7), 847-850. - Yuk, J.S., Kim, T., Cho, H., & Gwak, G. (2024). Breast cancer risk association with
postmenopausal hormone therapy: Health Insurance Database in South Korea-based cohort study.
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© Donna