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Evaluation of an individual patient to inform the most appropriate and beneficial personalized treatment is at the core of functional medicine. Perimenopausal and menopausal women are a large demographic group who may benefit from this approach, with each woman presenting a unique hormone profile, health history, and wellness path. Tailored interventions may help to alleviate symptoms and reduce long-term health risks associated with menopause by addressing any underlying issues that are known to contribute to hormone imbalances. These 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).
HRT: Current Research
Hormone replace 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 However, 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
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 Positive research data has been more supportive for bioidentical hormone regimens.12,14
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.15 Investigators also noted that the excess BRCA risks in the postmenopausal HRT users were strongly duration-dependent.15
Regarding cognitive health, a 2021 systematic review (N=4 meta-analysis and eight additional original studies that included cohort, RCT, and case-control studies) explored the relationship between menopausal hormone therapy and dementia development.13 Researchers found that a majority of studies suggested 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 2019.16 Researchers acknowledged inconsistent assessment results among studies and observed older study populations with more underlying diseases in RCTs compared to observational studies. With those noted stipulations, results indicated:16
- 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).
The reported summary estimates analyzed the combined measures of effect from the included RCTs, cohort, and case-control studies. Investigators also noted subgroup analysis results that indicated differing clinical effects depending on timing of HRT initiation, underlying disease, regimen type, and route of administration.16
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.17 Investigators reported that compared to baseline, HRT significantly:17
- 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 prevention must consider a patient’s individual benefit/risk profile. A collaborative patient-practitioner relationship is vital 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.
IFM’s “PTSD” mnemonic is a foundational principle for the assessment and treatment of all hormonal imbalances. This functional medicine approach identifies points of leverage where personalized interventions help to restore hormonal balance through the improvement of production, transport, sensitivity, and detoxification of hormones. 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 to 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.18-20 Stress management practices such as mindfulness, meditation, and yoga are other promising approaches to alleviating menopausal symptoms.21,22
A concurrent nutraceutical treatment may also provide foundational support. For example, evidence continues to gather regarding the benefit of phytoestrogens for menopausal symptoms. Isoflavones are phytoestrogens found in soybeans and other legumes, including red clover. A 2019 review found that despite varying isoflavone component and dosage, outcomes, and trial durations, overall study results suggested that isoflavones may help to reduce hot flashes, attenuate lumbar spine bone mineral density, benefit systolic blood pressure during early menopause, and improve glycemic control without safety profile concerns.23 Other studies continue to explore the anti-inflammatory benefits of a variety of phytoestrogens and the supportive bone-health properties of plants such as black cohosh, sage, and rhubarb for menopausal populations.24,25
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.
- The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of the North American Menopause Society. Menopause. 2017;24(7):728-753. doi:10.1097/GME.0000000000000921
- North American Menopause Society updates position statement on hormone therapy, says benefits outweigh risks for some women. BreastCancer.org. Updated February 22, 2022. Accessed April 29, 2022. https://www.breastcancer.org/research-news/nams-updates-hrt-position-statement
- Flores VA, Pal L, Manson JE. Hormone therapy in menopause: concepts, controversies, and approach to treatment. Endocr Rev. 2021;42(6):720-752. doi:10.1210/endrev/bnab011
- Academic Committee of the Korean Society of Menopause, Lee SR, Cho MK, et al. The 2020 Menopausal Hormone Therapy Guidelines. J Menopausal Med. 2020;26(2):69-98. doi:10.6118/jmm.20000
- Kapoor E, Kling JM, Lobo AS, Faubion SS. Menopausal hormone therapy in women with medical conditions. Best Pract Res Clin Endocrinol Metab. 2021;35(6):101578. doi:10.1016/j.beem.2021.101578
- Currie H. Managing menopausal symptoms-hormone replacement therapy is not the only option! Post Reprod Health. 2021;27(4):183-184. doi:10.1177/20533691211063191
- Armeni E, Paschou SA, Goulis DG, Lambrinoudaki I. Hormone therapy regimens for managing the menopause and premature ovarian insufficiency. Best Pract Res Clin Endocrinol Metab. 2021;35(6):101561. doi:10.1016/j.beem.2021.101561
- Rozenberg S, Di Pietrantonio V, Vandromme J, Gilles C. Menopausal hormone therapy and breast cancer risk. Best Pract Res Clin Endocrinol Metab. 2021;35(6):101577. doi:10.1016/j.beem.2021.101577
- Gosset A, Pouillès JM, Trémollieres F. Menopausal hormone therapy for the management of osteoporosis. Best Pract Res Clin Endocrinol Metab. 2021;35(6):101551. doi:10.1016/j.beem.2021.101551
- L’Hermite M. Bioidentical menopausal hormone therapy: registered hormones (non-oral estradiol ± progesterone) are optimal. Climacteric. 2017;20(4):331-338. doi:10.1080/13697137.2017.1291607
- Files J, Kling JM. Transdermal delivery of bioidentical estrogen in menopausal hormone therapy: a clinical review. Expert Opin Drug Deliv. 2020;17(4):543-549. doi:10.1080/17425247.2020.1700949
- Stute P, Wildt L, Neulen J. The impact of micronized progesterone on breast cancer risk: a systematic review. Climacteric. 2018;21(2):111-122. doi:10.1080/13697137.2017.1421925
- Stute P, Wienges J, Koller AS, et al. Cognitive health after menopause: does menopausal hormone therapy affect it? Best Pract Res Clin Endocrinol Metab. 2021;35(6):101565. doi:10.1016/j.beem.2021.101565
- Mikkola TS, Tuomikoski P, Lyytinen H, et al. Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality. Menopause. 2015;22(9):976-983. doi:10.1097/GME.0000000000000450
- Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet. 2019;394(10204):1159-1168. doi:10.1016/S0140-6736(19)31709-X
- Kim JE, Chang JH, Jeong MJ, et al. A systematic review and meta-analysis of effects of menopausal hormone therapy on cardiovascular diseases. Sci Rep. 2020;10(1):20631. doi:10.1038/s41598-020-77534-9
- Li S, Ma L, Song Y, et al. Effects of hormone replacement therapy on glucose and lipid metabolism in peri- and postmenopausal women with a history of menstrual disorders. BMC Endocr Disord. 2021;21(1):121. doi:10.1186/s12902-021-00784-9
- Hettchen M, von Stengel S, Kohl M, et al. Changes in menopausal risk factors in early postmenopausal osteopenic women after 13 months of high-intensity exercise: the randomized controlled ACTLIFE-RCT. Clin Interv Aging. 2021;16:83-96. doi:10.2147/CIA.S283177
- Quattrini S, Pampaloni B, Gronchi G, Giusti F, Brandi ML. The Mediterranean diet in osteoporosis prevention: an insight in a peri- and post-menopausal population. Nutrients. 2021;13(2):531. doi:10.3390/nu13020531
- Malmir H, Saneei P, Larijani B, Esmaillzadeh A. Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies. Eur J Nutr. 2018;57(6):2147-2160. doi:10.1007/s00394-017-1490-3
- Gordon JL, Halleran M, Beshai S, Eisenlohr-Moul TA, Frederick J, Campbell TS. Endocrine and psychosocial moderators of mindfulness-based stress reduction for the prevention of perimenopausal depressive symptoms: a randomized controlled trial. Psychoneuroendocrinology. 2021;130:105277. doi:10.1016/j.psyneuen.2021.105277
- Cramer H, Peng W, Lauche R. Yoga for menopausal symptoms—a systematic review and meta-analysis. Maturitas. 2018;109:13-25. doi:10.1016/j.maturitas.2017.12.005
- Chen LR, Ko NY, Chen KH. Isoflavone supplements for menopausal women: a systematic review. Nutrients. 2019;11(11):2649. doi:10.3390/nu11112649
- Vrachnis N, Zygouris D, Vrachnis D, et al. Effects of hormone therapy and flavonoids capable on reversal of menopausal immune senescence. Nutrients. 2021;13(7):2363. doi:10.3390/nu13072363
- Slupski W, Jawien P, Nowak B. Botanicals in postmenopausal osteoporosis. Nutrients. 2021;13(5):1609. doi:10.3390/nu13051609