Understanding Hormone Replacement Therapy (HRT)
Hormone Replacement Therapy (HRT) has been a widely debated topic in women’s health, particularly for managing menopausal symptoms such as hot flashes, night sweats, and mood swings. Recent research (see references and resources at end of post) has helped refine the understanding of HRT’s benefits and risks, leading to more personalized approaches to its use.
In this post, we discuss the information we found in our quest to understand HRT options and want to advise our readers considering HRT to discuss their individual risk factors and therapy options with a qualified healthcare provider before starting treatment.
HRT and Related Acronyms
HRT, the term we use in this post, is an umbrella term for hormone-based treatments used to manage menopausal symptoms. However, in your own journey to learn more, you may encounter related terms, including:
- MRT (Menopausal Replacement Therapy): A term sometimes used interchangeably with HRT, specifically emphasizing its role in managing menopause.
- BHRT (Bioidentical Hormone Replacement Therapy): Refers to hormones that are structurally identical to those naturally produced in the body.
- ET (Estrogen Therapy): Used alone for women who have had a hysterectomy or to manage menopausal symptoms like night sweats and vaginal dryness.
- EPT (Estrogen-Progestin Therapy): Combines estrogen and progestin to protect the uterus from endometrial cancer.
Benefits of HRT
Relief from Menopausal Symptoms
A study from the Southern Illinois University School of Medicine supports the use of HRT for managing menopausal symptoms, particularly when initiated in early menopause. The study indicates that hormone replacement therapy can significantly reduce the severity of symptoms like hot flashes and sleep disturbances.
Anti-Aging and Longevity Benefits
A recent publication in JAMA Network Open found that postmenopausal women who had used HRT appeared biologically younger than those who had not. Researchers observed that these women had longer telomeres—genetic markers associated with slower aging—which suggests potential long-term health benefits of HRT beyond symptom relief.
Bone and Heart Health
HRT has also been associated with a lower risk of osteoporosis and cardiovascular disease in certain populations. According to the National Institutes of Health (NIH), women under 60 (and according to an AHA study with a low-risk health profile) who begin HRT early in menopause may experience protective effects against heart disease and bone fractures.
Risks and Considerations
Breast and Ovarian Cancer Risk
Studies suggest that long-term use of combined estrogen and progestin therapy may slightly increase the risk of breast and ovarian cancers. The significant turning point in HRT research came with the Women’s Health Initiative (WHI) study in 2002, which led to a dramatic decline in HRT use due to concerns about increased breast cancer risk. However, newer and subsequent research has clarified that the risks were overstated for many women, particularly those who begin HRT before age 60 and with a low-risk health profile. Additionally, the Harvard Medical School has reviewed more recent research that indicates the risk of breast cancer from HRT is lower than initially believed, though it’s important to note that some risk still exists.
Cardiovascular Health Concerns
The use of HRT has seen significant changes in prescribing patterns since the early 2000s, largely due to concerns raised by the WHI study regarding cardiovascular risks from systemic HRT, hormones delivered through the bloodstream via pills, patches, injections, and pellets. Note that vaginal therapy is not considered systemic but instead localized. However, a more recent study by the American Heart Association (AHA) suggest that the cardiovascular risks of HRT may depend on the timing of initiation as well as a woman’s health profile. The study found that women with low risk health profiles who began HRT closer to menopause had a reduced risk of cardiovascular events compared to those who started therapy later. While HRT may have protective effects on the heart when initiated early, typically before age 60 or within 10 years of menopause onset, studies do indicate potential risks for women with certain health issues (see figure 3 in the linked AHA study) and who start HRT later in life.
HRT Cheat Sheet
HRT is often described as either bioidentical or synthetic hormones. It is important to understand the differences along with their risks.
Bioidentical Hormones are considered structurally identical to human hormones, often derived from plant sources. FDA-approved bioidentical hormones are just as regulated as synthetic hormones. However, custom-compounded versions lack FDA regulation and standardization.
Pros:
- Structurally identical to natural human hormones, potentially leading to better compatibility
- Customizable dosing through compounding pharmacies (for custom-compounded versions)
Cons:
- Lack of standardization and regulation in custom-compounded formulations, leading to potential quality and purity concerns
- Limited long-term studies on the safety and effectiveness of compounded BHRT
Who Might Choose BHRT?
- Individuals seeking hormones identical to those their bodies produce naturally
- Those interested in personalized dosing regimens
Synthetic Hormones are generally considered hormones that mimic natural hormones but may have slight structural differences. These are widely studied and FDA-regulated.
Pros:
- FDA-approved and rigorously tested for safety and efficacy
- Standardized dosages ensure consistent hormone levels
- Extensive research supports their benefits and risks
Cons:
- May cause side effects in some individuals due to molecular differences from natural hormones
- Some formulations have been linked to increased risks of blood clots and certain cancers, though risks depend on factors like age and duration of use
Who Might Choose Synthetic HRT?
- Individuals who prefer treatments with well-documented safety data
- Those who need standardized dosing without custom compounding
- Patients whose insurance covers synthetic formulations but not BHRT
Hormone therapy types are the hormones, estrogen only or estrogen-progesterone, offered in a prescription based on the woman’s symptoms and hysterectomy history.
Estrogen only is used primarily for women who have had a hysterectomy. Examples include Estradiol (Estrace, Climara), Conjugated Estrogens (Premarin).
Pros:
- Effective for hot flashes, vaginal dryness, and bone health
- Lower risk of breast cancer compared to combined therapy, though some studies suggest a small increased risk with long-term use
Cons:
- Increases the risk of endometrial cancer if the uterus is intact
- Potential increased risk of blood clots and stroke
Typically not recommended for:
- Women with a history of breast, ovarian, or endometrial cancer
- Those with blood clotting disorders or cardiovascular disease risk
Estrogen-Progesterone (EPT) is used primarily for women with a uterus to prevent endometrial hyperplasia. Examples include Estradiol + Norethindrone (Activella), Conjugated Estrogens + Medroxyprogesterone (Prempro).
Pros:
- Protects against endometrial cancer
- Effective for a broad range of menopausal symptoms
Cons:
- Slightly increased risk of breast cancer with long-term use
- Higher risk of blood clots and stroke
Typically not recommended for:
- Women with a history of breast cancer, stroke, or blood clots.
The Administration / application of hormone therapy comes in a range of options but depending on the hormone therapy that is right for you, your options may be limited.
Oral HRT is taken in pill form. Examples include Estradiol (Estrace), Conjugated Estrogens (Premarin).
Pros:
- Convenient and widely available
Cons:
- Higher risk of blood clots due to liver metabolism
Typically Not Recommended For:
- Women with a history of blood clots or liver disease
- Those at high risk for stroke or cardiovascular disease
Topical HRT (Transdermal, Vaginal, Gels, Creams, Patches) is applied and absorbed through the skin or mucosal tissue. Examples include Estradiol Patch (Vivelle-Dot, Climara), Estradiol Gel (Divigel, Estrogel), Vaginal Cream (Premarin, Estrace).
Pros:
- Bypasses the liver, reducing the risk of blood clots
- Provides a steady hormone dose
Cons:
- Skin irritation is possible
- May be more expensive than oral options
Typically not recommended for:
- Women with skin sensitivities or allergies to adhesives
Injectable Therapy involves administering hormones via intramuscular or subcutaneous injections. These injections provide a steady release of hormones into the bloodstream. Examples include Depo-Estradiol, Delestrogen.
Pros:
- Direct absorption, bypassing liver metabolism
- Steady and consistent hormone levels
- Less frequent dosing compared to oral or topical methods
Cons:
- Requires administration by a healthcare provider
- Potential for site reactions or discomfort at the injection site
- Less flexibility in dose adjustments once administered
Typically not recommended for:
- Women who prefer self-administered or more consistent daily dosing options
- Women with clotting disorders or a history of thromboembolic events
- Women who are uncomfortable with needles or injections
- Women with liver disease, as hormone metabolism may still be affected
Pellet therapy involves inserting small, rice-sized pellets under the skin, typically in the hip area. These pellets release hormones steadily over several months. Examples include BioTE, SottoPelle, HormonePellets.
Pros:
- Provides a steady release of hormones over time
- Long-lasting effects, with pellets typically replaced every 3-6 months
- No need to remember daily pills or apply topical products
Cons:
- Requires a minor surgical procedure for insertion
- Difficulty in adjusting hormone levels once inserted
- Potential for site reactions, including infection or pellet extrusion
Typically not recommended for:
- Women with fluctuating hormone needs require frequent dose adjustments
- Those prone to keloids or poor wound healing
- Individuals uncomfortable with surgical procedures
Individualized Treatment Approach
Currrently, healthcare professionals emphasize the importance of an individualized approach to HRT. It’s essential to consult with a healthcare provider to determine the most suitable HRT option based on your individual health profiles and risk factors.
Doing your own research is part of developing a comprehensive understanding so you can have an informed conversation with your provider about the benefits and risks associated with HRT. Below is a list of resources used for this post that you may find helpful.
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This post was researched and drafted with the assistance of AI. All sources were reviewed and verified to the best of their ability by the editorial team.
Disclaimer: This blog is intended for informational purposes only and should not be considered legal or medical advice, diagnosis, or treatment. We strongly encourage readers to conduct their own research and consult with a qualified healthcare professional before making any decisions or changes to their health and medical routines. Marigold Brands and The Marigold Woman cannot be held accountable for any inaccuracies or adverse outcomes related to the information presented. We strive to provide accurate and up-to-date information. However, medical knowledge is constantly evolving, and individual experiences may vary. Sources and references are provided to support the content and enable readers to further explore topics and do not imply endorsement. Always consult with your healthcare provider before making significant changes to your health routine.
References and Resources
HRT
Southern Illinois University School of Medicine. (2024, July 16). New study supports hormone replacement therapy early menopause. SIU Medicine Blog. https://www.siumed.edu/blog/new-study-supports-hormone-replacement-therapy-early-menopause
JAMA Network. (2023). Hormone replacement therapy study. JAMA Network Open. https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2822953
National Institutes of Health. (2024, May 1). Researchers review findings and clinical messages from the Women’s Health Initiative 30 years after launch. NIH. https://www.nih.gov/news-events/news-releases/researchers-review-findings-clinical-messages-women-s-health-initiative-30-years-after-launch
American Heart Association. (2024). Hormone replacement therapy and cardiovascular health. Circulation. https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.061559
National Center for Biotechnology Information. (2019, Sept. 19). The Controversial History of Hormone Replacement Therapy. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC6780820/
Harvard School of Public Health. (2023, Feb. 10). Hormone therapy benefits may outweigh risks for many younger menopausal women. HSPH News. https://hsph.harvard.edu/news/hormonal-therapy-menopause/
JAMA Health Forum. (2024, Sept. 27). Recent Trends in Menopausal Hormone Therapy Use in the US Insights, Disparities, and Implications for Practice. JAMA Health Forum. https://jamanetwork.com/journals/jama-health-forum/fullarticle/2823978
Mayo Clinic. (2022, Dec. 6). Hormone therapy: Is it right for you? Mayo Clinic. https://www.mayoclinic.org/hormone-therapy/art-20046372
National Center for Biotechnology Information. (2024, Oct. 6.). Hormone Replacement Therapy. NIH Website. https://www.ncbi.nlm.nih.gov/books/NBK493191
U.S. Food and Drug Administration. (2019, Aug. 22). Menopause: Medicines to Help You. FDA Consumer Information. https://www.fda.gov/consumers/free-publications-women/menopause-medicines-help-you
American College of Obstetricians and Gynecologists. (2021, Oct.). Hormone Therapy for Menopause. ACOG Women’s Health FAQs. https://www.acog.org/womens-health/faqs/hormone-therapy-for-menopause
National Center for Biotechnology Information. (2021, Mar. 26). Risks, Benefits, and Treatment Modalities of Menopausal Hormone Therapy: Current Concepts. PMC. https://pmc.ncbi.nlm.nih.gov/articles/PMC8034540/
Cleveland Clinic. (2024, Apr. 12.). Hormone Therapy for Menopause Symptoms. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/15245-hormone-therapy-for-menopause-symptoms
Canadian Cancer Society. (n.d.). All about hormone replacement therapy (HRT). Cancer Information. https://cancer.ca/en/cancer-information/reduce-your-risk/understand-hormones/all-about-hormone-replacement-therapy-hrt
Bioidentical Hormones
Harvard Health Publishing. (2022, Jan. 1). Are bioidentical hormones superior to hormone medications? Harvard Health. https://www.health.harvard.edu/womens-health/are-bioidentical-hormones-superior-to-hormone-medications
Cleveland Clinic. (2022, Apr. 15). Bioidentical Hormones. Cleveland Clinic. https://my.clevelandclinic.org/health/treatments/15660-bioidentical-hormones
Mayo Clinic. (2024, Oct. 03.). Bioidentical Hormones: Are They Safe? Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/menopause/expert-answers/bioidentical-hormones/faq-20058460
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