Menopause Hormone Therapy: Weighing Benefits & Risks

Perimenopausal and menopausal women are a large demographic group, with each woman presenting a unique hormone profile, health history, and wellness path. Evaluation of each patient to inform the most appropriate and beneficial personalized health strategy is at the core of functional medicine. Tailored interventions may help alleviate menopausal symptoms and reduce long-term health risks associated with menopause by addressing any underlying issues that are known to contribute to hormone imbalances. Interventions may include nutraceutical and lifestyle treatments, hormone replacement therapies, or a combination of approaches.

When considering menopausal hormone therapy, how can you best weigh the benefits and risks for your individual patients?

In the following video, IFM’s Director of Medical Education Dan Lukaczer, ND, IFMCP, highlights the functional medicine approaches to menopause that are further detailed at IFM’s Hormone Advanced Practice Module (APM).

(Video Time: 2 minutes) As the director of Medical Education at IFM, Dr. Lukaczer oversees IFM Certification Programs, CME accreditation, and IFM’s Annual International Conference. He previously served as the director of Clinical Research at Metagenics’ Functional Medicine Research Center, where he was the principal investigator on various clinical trials on diet and nutrition

Hormone Replacement Therapy: The Current Research

Hormone replacement therapy (HRT) use during the menopause life stage has documented advantages and disadvantages. Research studies and recommendations in recent medical literature indicate that HRT is an effective therapy with benefits that outweigh risks for women without comorbidities who are younger than 60 years and/or who have been in menopause for less than 10 years.^1-5 In addition, HRT has been suggested as a prioritized intervention for otherwise healthy women who experience early or premature menopause due to this population’s elevated lifetime risk for chronic conditions linked to ovarian hormone deficiency.^3,6

Due to increased risks for some populations of women, there is also a well-documented emphasis on personalized interventions and a recognized clinical need to understand all health factors for an individual patient when discussing and prescribing HRT for menopause symptoms and health risk prevention.^3,4,6-9

In addition to dosage, duration, and route of administration, another important factor to consider is the type of hormone used in treatment. Research studies have suggested that differing effects and safety profiles may be encountered based on the hormone source (e.g., bioidentical hormones such as estradiol and micronized progesterone versus other hormone types such as conjugated equine estrogens or synthetic progestogens).^4,10-13 Research data has generally been supportive of bioidentical hormone regimens.^12,14-16

Breast Cancer, Dementia, and Cardiometabolic Health

The relationship between HRT and chronic disease outcomes is influenced by age-specific impacts and the duration, dosage, type, and route of administration.^4,5 A 2019 systematic review looked at hormone therapy and breast cancer (BRCA) risk (n=59 prospective studies with 143,887 postmenopausal women with BRCA and 424,972 without) and echoed previous studies, finding an overall increased risk for those who used HRT compared to those who did not, with greater risk for those who used estrogen-progestogen versus estrogen-only preparations.¹⁷ Investigators noted that the excess BRCA risks in the postmenopausal HRT users were strongly duration-dependent.¹⁷

Regarding cognitive health, a 2021 systematic review (n=4 meta-analyses plus eight additional original studies) explored the relationship between menopausal hormone therapy and dementia development.¹³ A majority of the included studies suggested hormone therapy was associated with an 11 to 33% dementia risk reduction in women without pre-existing dementia.¹³ The degree of benefit appeared to vary depending on therapy type and age at initiation.

A 2020 meta-analysis assessed the association between menopausal hormone therapy and cardiovascular disease (CVD) and included 26 randomized controlled trials (RCTs) and 47 observational studies published between 2000 and 2019.¹⁸ Researchers acknowledged inconsistent assessments among studies. The RCTs included older study populations with more underlying diseases compared to the observational studies. With those noted stipulations, results indicated:¹⁸

• Increased risk of venous thromboembolism in both RCTs (summary estimate (SE): 1.70, 95% CI: 1.33-2.16) and observational studies (1.32, 1.13-1.54).
• Increased risk of stroke in RCTs (1.14, 1.04-1.25).
• Decreased risk of myocardial infarction in observational studies (0.79, 0.75-0.84).

Investigators also noted different clinical effects in subgroup analysis depending on timing of HRT initiation, underlying disease, regimen type, and route of administration.¹⁸

Furthering the discussion on cardiometabolic health, a 2021 observational study (n=595 peri- and postmenopausal women divided into normal or menstrual disorder groups) measured glucose and lipid metabolism indicators at baseline and after six to twelve months of HRT.¹⁹ Investigators reported that compared to baseline, HRT significantly:¹⁹

• Decreased fasting insulin and insulin resistance in perimenopausal users.
• Decreased fasting glucose levels in postmenopausal users with prior menstrual disorders.
• Decreased low-density lipoprotein (LDL) cholesterol, total cholesterol, fasting insulin and glucose, and insulin resistance in both peri- and postmenopausal women without previous menstrual disorders.

Personalized Treatment Considerations

While general clinical guidelines help us to understand some of the conflicting research, potential therapies for the treatment of menopausal symptoms and life-long health must consider a patient’s individual benefit/risk profile. A collaborative patient-practitioner relationship is essential not only for discussing hormone treatment benefits and risks but also supporting the patient’s personal preferences. Helping women optimize the benefits of healthy hormones through the functional medicine model is a vital step forward for women’s health.

One of IFM’s tools specific to menopause is the Menopause Decision Tree. This resource provides an additional guide for assessing an individual patient’s menopausal symptoms and health goals within the context of their complete health story. Identifying menopausal patterns and wellness concerns helps inform an appropriate intervention. Modifiable lifestyle factors such as nutrition and exercise are at the core of the functional medicine approach, and these interventions have been shown to positively support menopause-related health issues.^20-22 Stress management practices such as mindfulness, meditation, and yoga are other promising approaches to alleviating menopausal symptoms.^23,24 A concurrent nutraceutical treatment may also provide foundational support. For example, evidence continues to gather regarding the benefit of phytoestrogens for menopausal symptoms as well as bone health.^25-29

Conclusion

Recognizing menopause-related patterns within the context of a patient’s health story helps clinicians to customize the most appropriate and beneficial treatment plan for each individual. IFM’s Menopause Decision Tree is just one tool that is accessible to help clinicians and their patients navigate treatment options. Learn more at IFM’s upcoming Hormone Advanced Practice Module (APM), where functional medicine experts will examine the evidence for the use of hormone and non-hormone treatments, detail the steroidogenic pathways for hormone production and metabolism, and elucidate the other systems that commonly interplay with hormone health.