Women’s Hormone Therapy: What We Know, What We Don’t, and What Matters Most
💡 This article is the second in our Hormone Health series. The first post covered the broader history and evidence behind HRT. This one focuses on women—how hormones change in peri- and post-menopause, and how estrogen, progesterone, and testosterone can be used safely and effectively.
Quick Takeaway
Hormone therapy (HRT) can safely help many women in perimenopause, menopause, and postmenopause — when prescribed thoughtfully and monitored. ¹–³
For women at average risk (meaning no personal or strong family history of breast cancer), the lifetime risk of developing breast cancer is about 1 in 8 (roughly 12%).
Taking a combined estrogen and progestin therapy — like the type used in the Women’s Health Initiative (WHI) study — adds about 8 extra breast cancer cases per 10,000 women per year (an increase of roughly 0.08% each year).
This small change must be weighed against each woman’s symptoms, goals, and personal risk factors. It does not apply to women taking estrogen-only therapy after hysterectomy, which showed lower breast-cancer incidence and mortality in follow-up studies. ¹,²,²⁸The WHI raised concerns two decades ago, but newer evidence shows risks depend on timing, age, dose, and route. ¹–⁵
Estrogen, progesterone, and (in select cases) testosterone can improve energy, sleep, brain fog, mood, libido, and long-term bone and heart health. ³ ⁶–⁹ ¹⁸ ¹⁹
Compounded “bioidentical” hormones can expand access (for example, low-dose testosterone for women) but lack the standardized safety data of FDA-approved products. Always use a trusted compounding pharmacy that meets strict quality and testing standards. ³ ¹⁶
Maintaining muscle, healthy weight, and good sleep supports hormone balance — but these are not substitutes for HRT when symptoms are significant. ²⁰–²³
The best plan is individualized — built around your biology, goals, and safety markers, with regular follow-up. ³ ⁷ ¹⁰ ¹²
It’s never “too late” to discuss HRT. Starting early—around the time hormones begin to decline—can maximize benefits, but even starting later may still improve quality of life and certain health outcomes when done carefully. ³ ⁴ ⁵ ²⁸
Why This Matters
Too many women spend years being told their brain fog, mood shifts, and sleep disruption are “normal.” Modern evidence confirms that the hormone decline of menopause is a systemic change affecting the brain, heart, bones, and metabolism—not just hot flashes. As Dr. Rachel Rubin emphasized on The Drive with Peter Attia, menopause affects the brain, bladder, bones, and relationships. ¹¹
Guidance from NAMS, NIH, and the Endocrine Society affirms that appropriately timed HRT is both safe and effective for many women. ¹–³ ⁶ ⁷ ¹⁰
The WHI: What It Really Showed
Early WHI headlines suggested HRT caused breast cancer and heart disease. ¹ Looking closer:
In the WHI, women who took a combination of estrogen and progestin (specifically conjugated equine estrogen with medroxyprogesterone acetate) had about 8 additional breast cancer cases per 10,000 women per year—an annual increase of roughly 0.08%. This small change needs to be weighed against each woman’s symptoms, goals, and baseline health risks. ¹
Participants were older (average 63)—well past the typical transition—so baseline CVD/cancer risks were higher. Timing matters: starting closer to menopause is associated with more favorable cardiovascular outcomes. ² ⁴ ⁵
Long-term follow-up showed no increase in all-cause mortality overall; women closer to menopause had neutral or even improved cardiovascular outcomes. ² ⁴ ⁵
Estrogen-only therapy (after hysterectomy) did not raise breast-cancer risk and may lower it in some groups; extended follow-up showed lower breast-cancer incidence and mortality vs placebo. ² ⁴ ⁵ ²⁸
Modern consensus (NAMS 2022) emphasizes a “window of opportunity”: start before age 60 or within ~10 years of menopause for the best benefit-risk balance. ³–⁵
Understanding the Transition & Timing
Hormone changes are not static; the phase of your transition helps define whether the goal of therapy is support or replacement.
Perimenopause
Estrogen and progesterone fluctuate, driving irregular cycles, hot flashes, sleep/mood changes, and brain fog; testosterone also begins to decline, affecting libido, energy, and muscle maintenance. In this phase, therapy often acts as support, smoothing fluctuations rather than fully replacing hormones. ³ ⁶ ¹⁸
Postmenopause
After 12 months without a period, estrogen remains low and stable. By this stage, therapy becomes true replacement, restoring hormones to physiologic levels that protect bone, cardiovascular, and sexual health while alleviating chronic symptoms of deficiency. ³ ¹²
Persistently low hormones increase risks of bone loss, atherosclerosis, and cognitive decline; starting HRT within the timing window can mitigate several of these risks for appropriate candidates. ³ ⁶–⁹
Recognizing Hormone Deficiency Symptoms
Every woman’s experience is unique. Not everyone will have all—or any—of these symptoms. Knowing the patterns helps guide testing and discussion.
Estrogen Deficiency (common signs)
Hot flashes and night sweats
Mood changes or anxiety
Sleep disturbance or insomnia
Cognitive “fog” or forgetfulness
Vaginal dryness or pain with intercourse
Urinary urgency or recurrent UTIs
Palpitations or irregular heartbeats
Dry eyes, thinning hair, or increased skin sensitivity
Heightened allergies or inflammation
Testosterone Deficiency (common signs)
Reduced libido or clitoral insensitivity
Weight gain or difficulty losing fat
Fatigue or slow recovery after workouts
Muscle loss or aches
Reduced motivation or focus
Worsened insulin sensitivity
Occasionally, new-onset migraines
These symptoms can overlap with thyroid, sleep, or stress-related issues—another reason thorough evaluation and individualized testing matter before starting treatment.
What We Know
Symptom relief: HRT is the most effective treatment for vasomotor symptoms and genitourinary syndrome of menopause (GSM). ³ ¹² ¹³
Bone health: Estrogen reduces fracture risk and slows bone loss. ⁶
Heart health: Early initiation supports vascular function and may improve lipids; route matters. ⁷–⁹
Metabolism & body composition: Estrogen and carefully selected low-dose testosterone help preserve lean mass, support insulin sensitivity, and reduce visceral fat in some women. ⁷ ¹⁸ ¹⁹ ²³
What We Don’t Fully Know
Cognition/dementia: WHIMS suggested late initiation (≥65) may be unfavorable; newer data are evolving and warrant ongoing review. ¹⁴ ¹⁵
Duration and targets (“optimal ranges”): Most guidelines still emphasize relief of symptoms with safety monitoring rather than chasing a single lab number. ³ ¹⁰
That said, a growing number of clinicians personalize therapy toward functional targets within physiologic ranges (not supraphysiologic) to support muscle health, mood, memory, sleep, sexual function, and insulin sensitivity, especially when symptoms persist despite “normal” labs. Evidence for hard outcomes and longevity endpoints is still limited and mixed, so any “optimization” approach should be individualized, time-limited trials with clear goals, side-effect checkpoints, and regular labs. ³ ⁷ ¹⁸ ¹⁹Compounded bioidenticals/pellets: Can offer customization or access but lack standardized safety/efficacy data vs FDA-approved products; use only with verified pharmacies and clinician oversight. ³ ¹⁶
Treatment Modalities: Know Your Options
Hormone therapy isn’t one-size-fits-all. The “best” choice depends on your symptoms, age, medical history, and goals. The key is to know your options and decide together with your clinician.
Estrogen
Transdermal: patches, gels, creams ⁷ ¹² ¹⁷
Oral: tablets ⁷ ¹² ¹⁷
Pellets: subdermal implants placed periodically ³ ¹⁶
Vaginal/local: creams, tablets, rings (for vaginal/urinary symptoms) ¹² ¹³
Progesterone
Oral micronized progesterone (often at bedtime) ³ ¹² ²⁴
Intrauterine system (IUD) for endometrial protection in select cases
Combination products (estrogen + progestogen)
Topicals/creams (discuss reliability for uterine protection with your clinician) ³
Testosterone (for select women)
Topical: creams or gels (low-dose, titrated) ¹⁸ ¹⁹
Injectables ¹⁸
Pellets ¹⁶ ¹⁸
Adjunct & Non-Hormonal Options
Local vaginal moisturizers/lubricants (non-hormonal)
Non-hormonal therapies for hot flashes, mood, or sleep (discuss individually)
Monitoring & Labs: What to Expect
Safe, effective HRT means tracking both symptoms and labs. The goal is consistent, personalized follow-up—not “set it and forget it.”
Before starting: Baseline labs and medical review.
~4 weeks after starting or changing therapy: Recheck labs and adjust dose as needed.
Once stable: Every 3–6 months, depending on the situation.
Ongoing: Preventive screening (mammogram per guidelines, lipids, etc.) and medication check-ins. ³ ¹⁰ ¹²
Who Is Not a Good Candidate for Systemic HRT?
While many women benefit, there are situations where systemic estrogen/progestogen (and sometimes testosterone) should be avoided. ³ ³¹
Absolute or near-absolute contraindications include:
Pregnancy or breastfeeding
Active breast cancer or other estrogen/progestogen-dependent cancers
Unexplained vaginal bleeding (evaluate before starting) ³ ³¹
Acute thromboembolic disorder (DVT/PE) or very recent stroke ³ ³¹
Very recent myocardial infarction or unstable/high-risk cardiovascular disease ³ ³¹
Severe active liver disease or significant hepatic dysfunction ³ ³¹
Severe, decompensated renal or cardiac disease (until stabilized) ³¹
These apply primarily to systemic HRT. Low-dose local vaginal estrogen for GSM may still be appropriate with specialist input due to minimal systemic absorption. ³ ¹²
Testosterone in women: Avoid during pregnancy/breastfeeding and in androgen-sensitive cancers; use only for defined indications with monitoring. ¹⁸ ¹⁹
Supplements and Hormone Therapy: What’s Worth Considering
Many women are told they “need” a stack of supplements to make hormone therapy work. In reality, for most healthy women on properly dosed and monitored HRT, additional supplements offer very little added benefit—think of them as a drop of water in a bucket compared to HRT’s effect size.
Commonly marketed options:
DIM (diindolylmethane): Sometimes used short-term when starting estrogen to help with mild tenderness or bloating; typically not needed long-term.
Ashwagandha: An adaptogenic herb promoted for stress, sleep, or libido; evidence is mixed and dosing varies widely.
Bottom line: supplements can occasionally play a short-term supportive role, but they’re not required for HRT to be effective. Discuss any products with a clinician who understands hormone therapy—some can alter hormone metabolism or labs. Keep your plan simple, evidence-based, and personalized.
Lifestyle and Preventive Care
Build/keep muscle: Resistance training improves insulin sensitivity and supports healthy body composition. ²⁰–²²
Maintain a healthy weight: Adipose tissue affects estrogen balance; extremes in either direction can worsen symptoms/metabolic risk. ²¹ ²³
Sleep & stress: Optimizing sleep and stress blunts cortisol-driven symptom amplification. ²⁶ ²⁷
Screen regularly: Mammograms, lipids, and appropriate labs should be reviewed at least annually while on therapy. ³ ¹⁰ ¹²
📌 Bottom Line
Menopause is natural—suffering through it isn’t. For women at average risk, the baseline lifetime risk of breast cancer is ~12% (1 in 8). While combined hormone therapy adds a small annual risk in WHI (~0.08%/yr), decisions should be individualized and balanced against symptom burden and goals. When started at the right time and monitored, modern HRT can significantly improve symptoms, preserve bone and heart health, and support cognitive and emotional well-being. ¹–⁹ ¹² ¹³
At ZinovyMed, we pair individualized HRT with biomarker tracking, preventive labs, and concierge-level follow-up—helping women move through menopause with clarity, strength, and vitality.
References
Rossouw JE, et al. JAMA. 2002;288:321–333.
Manson JE, et al. JAMA. 2017;318:927–938.
NAMS 2022 Position Statement. Menopause. 2022;29:767–794.
Hodis HN, Mack WJ. Menopause. 2019.
Lobo RA, et al. Climacteric. 2022.
Wells GA, et al. Estrogen for fracture prevention. Cochrane Database Syst Rev. 2021.
Boardman HM, et al. HRT & CVD outcomes. Cochrane Database Syst Rev. 2015.
Henderson VW. Estrogens & cognition. Nat Rev Endocrinol. 2022.
Estrogen & cardiovascular outcomes review. Circulation. 2019.
Endocrine Society CPG (menopause/testosterone context). J Clin Endocrinol Metab. 2018.
Rubin R with Attia P. The Drive Podcast. 2023.
AUA Guideline on Genitourinary Syndrome of Menopause. 2025.
Constantine GD, et al. Vaginal estrogen outcomes. Menopause. 2019.
Espeland MA, et al. WHIMS. Neurology. 2004;62:1945–1951.
Henderson VW, et al. Timing hypothesis & cognition. Alzheimers Dement. 2016.
NAMS statement on compounded hormones/pellets. Menopause. 2022.
Canonico M, et al. Transdermal vs oral & VTE. BMJ. 2008.
Davis SR, et al. Global Consensus on Testosterone Therapy for Women. Lancet Diabetes Endocrinol. 2019.
Wierman ME, et al. Androgen therapy in women. J Clin Endocrinol Metab. 2014.
Phillips SM, Jäger R. Protein & muscle in aging women. Nutrients. 2022.
Lovejoy JC. Menopause, metabolism & weight. Obes Manag. 2009.
Daly RM, et al. Resistance training & bone. Osteoporos Int. 2014.
Mauvais-Jarvis F, et al. Sex hormones & metabolism. Endocr Rev. 2017.
Caufriez A, et al. Micronized progesterone & sleep. J Clin Endocrinol Metab. 2011.
Sacks FM, et al. Dietary fat & lipids. Circulation. 2020.
Baker FC, et al. Sleep across menopause. Menopause. 2019.
Thurston RC, et al. Vasomotor symptoms & sleep. Sleep Med. 2023.
Chlebowski RT, Anderson GL, Aragaki AK, et al. Estrogen alone and breast-cancer incidence and mortality in postmenopausal women: WHI follow-up. JAMA Oncol. 2020;6(2):295–305.
Collaborative Group on Hormonal Factors in Breast Cancer. Type and timing of menopausal hormone therapy and breast-cancer risk: meta-analysis of 58 studies. Lancet. 2019;394(10204):1159–1168.
Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer with different HRT: E3N cohort. Breast Cancer Res Treat. 2008;107(1):103–111.
Stuenkel CA, Davis SR, Gompel A, et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015;100(11):3975.
⚠️ Medical Disclaimer: This blog is for educational purposes only and is not a substitute for professional medical advice. Always consult your physician before starting or changing hormone therapy.
