Dr. Rachel Rubin on Women's Sexual Health, Menopause, and Hormone Replacement Therapy

In this episode of The Drive Podcast, host Peter Attia is joined by Dr. Rachel Rubin, a board-certified urologist and a leading expert in sexual health for both men and women. The conversation focuses extensively on women's sexual health, particularly the often-misunderstood topics of perimenopause, menopause, and the critical role of Hormone Replacement Therapy (HRT). Dr. Rubin provides a comprehensive overview of the hormonal changes women experience, the significant health risks associated with menopause beyond common symptoms, the flawed history of the Women's Health Initiative (WHI) study, and evidence-based approaches to using estrogen, progesterone, and testosterone in women. The episode also highlights the profound benefits of local vaginal hormone therapies and addresses the systemic failures and biases within healthcare that have led to the neglect of women's menopausal health. This discussion is highly relevant for women approaching or experiencing menopause, their partners, and healthcare professionals seeking to deepen their understanding of this critical aspect of women's well-being.

Key Insights

• Menopause is a significant "castration event" where ovarian hormone production (estrogen, progesterone, and testosterone) ceases, leading to an "empty gas tank." This has wide-ranging health implications far beyond hot flashes, including increased risks of osteoporosis, cardiovascular disease, dementia, cognitive decline, and recurrent urinary tract infections.
• The 2002 Women's Health Initiative (WHI) study, particularly its initial alarming press conference about HRT risks, was significantly misinterpreted. Its design flaws (using older populations and non-bioidentical hormones) led to decades of fear-based medicine, depriving millions of women of beneficial HRT. Notably, the estrogen-only arm of the WHI showed a decreased risk of breast cancer.
• Modern, individualized systemic Hormone Replacement Therapy—often utilizing transdermal estradiol, micronized progesterone (if a uterus is present), and physiologic doses of testosterone—can substantially improve quality of life, effectively manage menopausal symptoms, and offer long-term protection against chronic diseases. Personalized care and understanding the nuances of different hormone formulations and delivery methods are essential.
• Testosterone is a critically important hormone for women throughout their lives, not just around menopause, impacting libido, mood, energy, muscle health, and genitourinary function. Its decline typically begins in a woman's 30s and its replacement, though often overlooked, can be transformative for well-being.
• Local vaginal hormone therapy (using low-dose estrogen or DHEA) is an extremely safe, inexpensive, and highly effective treatment for Genitourinary Syndrome of Menopause (GSM). It significantly prevents urinary tract infections, alleviates vaginal dryness and pain with intercourse, improves urinary symptoms, and dramatically enhances quality of life, even for women on systemic HRT or those with traditional contraindications to systemic therapies.
• A profound and systemic lack of education and training exists among medical professionals regarding menopause management. This has resulted in widespread under-treatment, misinformation, and a failure to offer evidence-based care, forcing patients to become strong advocates for their own health.
• The healthcare system, including regulatory bodies like the FDA and the pharmaceutical industry, has historically deprioritized women's health research, particularly concerning menopause and female-specific hormone therapies. This has created significant barriers to optimal care and perpetuated outdated practices.

Understanding Menopause and Perimenopause: The "Empty Gas Tank"

Dr. Rachel Rubin, a urologist specializing in sexual health, explains that urologists are inherently quality-of-life doctors, dealing with urination and sexual medicine for all genders. She emphasizes the stark difference in hormonal decline between men and women. While men experience a gradual decrease in hormones (a "low gas tank"), women undergo menopause around age 52, which Dr. Rubin describes as a "castration event" where the "gas tank is officially empty." The ovaries cease to produce significant amounts of estrogen, progesterone, and testosterone.

Perimenopause, the transition period, is characterized by erratic hormone fluctuations – the "gas tank is over full and then it goes to empty really quickly without warning." During healthy reproductive years, estradiol might cycle from a low of around 50 picograms per milliliter (pg/mL) to a peak of 150-200 pg/mL during ovulation. In contrast, during perimenopause, these levels can swing wildly; Dr. Rubin cited a patient whose estrogen went from 200 pg/mL on day one of her cycle to 900 pg/mL by day ten. This chaos is due to the brain (via Follicle-Stimulating Hormone, FSH, and Luteinizing Hormone, LH) trying to stimulate aging ovaries, which sometimes over-respond or fail to respond predictably. Progesterone is primarily produced in the second half of the menstrual cycle (luteal phase) after ovulation. Sensitivity to progesterone and its withdrawal (causing PMS symptoms) varies greatly among women, likely due to differences in GABA receptor sensitivity in the brain.

The Far-Reaching Health Risks of Menopause

Dr. Rubin stresses that the risks of *not* taking hormone therapy are often overlooked. Menopause leads to significant health risks beyond the commonly known vasomotor symptoms like hot flashes and night sweats. These include:

• Genitourinary Syndrome of Menopause (GSM): As hormones decline, the vaginal and bladder microbiome changes, decreasing tissue acidity. This leads to an increased risk of recurrent urinary tract infections (UTIs), which can be serious and even fatal in older women. Other GSM symptoms include vaginal dryness, pain with intercourse (dyspareunia), urinary frequency, and urgency.
• Osteoporosis: The loss of estrogen accelerates bone density loss, significantly increasing the risk of fractures. Dr. Rubin notes that hip fractures carry a mortality risk comparable to breast cancer, and survivors often experience a permanent decline in quality of life.
• Dementia and Alzheimer's Disease: These conditions are more prevalent in women, and while the direct protective role of HRT on cognition is still debated, hormone loss is a contributing factor to brain health decline.
• Cardiovascular Disease: Heart disease is the number one killer of women, and risks escalate after menopause.
• Colon Cancer: The risk of colon cancer also increases in the absence of estrogen.
• Mental Health: While perimenopausal hormonal volatility can be particularly harsh on mental health, the "empty gas tank" of menopause continues to impact mood, anxiety, and cognitive function (brain fog).
• Musculoskeletal Symptoms: Joint pain, frozen shoulder, and plantar fasciitis are common due to the loss of hormones, which Dr. Rubin likens to the body's natural "joint fluid" or anti-inflammatory agents.

The Women's Health Initiative (WHI) Debacle: A Generation Misled

The conversation delves into the history of HRT and the profound negative impact of the Women's Health Initiative (WHI) study. HRT was a relatively standard practice until 2002, when a WHI press conference announced the early termination of the estrogen-plus-progestin arm due to perceived increased risks of breast cancer, blood clots, and cardiovascular disease. This led to an immediate and drastic decline in HRT use.

Dr. Rubin and Peter Attia highlight several critical flaws and misinterpretations of the WHI data:

• Hormone Formulation: The study used conjugated equine estrogens (Premarin) and a synthetic progestin (medroxyprogesterone acetate, or MPA, in Prempro), not the bioidentical estradiol and micronized progesterone commonly used today.
• Breast Cancer Risk: The reported 24% relative increase in breast cancer incidence in the estrogen-plus-progestin arm translated to a mere 0.1% absolute risk increase (one additional case per 1,000 women per year), with no increase in breast cancer mortality. This increased risk was primarily associated with the synthetic progestin (MPA). Crucially, the estrogen-only arm of the WHI (for women without a uterus) showed a *decreased* risk of both getting and dying from breast cancer, a finding that received little media attention.
• Ignored Benefits: The study also showed significant benefits in the HRT arms, including decreased risks of colon cancer, fractures, and diabetes, as well as a decrease in overall mortality.
• Cardiovascular Data: The initial cardiovascular concerns were largely overblown and did not hold up over longer-term analysis, especially when considering the older average age of participants (63 years) and the known risks of oral estrogens in this demographic.

The aftermath of the WHI was catastrophic: an estimated 20 million women were deprived of the benefits of HRT, leading to preventable morbidity and mortality. Furthermore, an entire generation of physicians was not adequately trained in menopause management, creating a "brain drain" as knowledgeable older doctors retired. Dr. Rubin notes that less than 6% of internal medicine, OB/GYN, or family practice residents receive even one hour of menopause education. This has perpetuated fear-based medicine and left women struggling to find informed care.

Modern Approaches to Hormone Replacement Therapy (HRT)

Dr. Rubin advocates for an individualized approach to HRT, emphasizing that therapy should be guided by a woman's symptoms, with lab tests used to help refine treatment rather than dictate it rigidly. The goal is to "fill the gas tank" appropriately.

Progesterone: If a woman has a uterus, progesterone is essential to protect the endometrial lining from hyperplasia and cancer. Micronized progesterone (e.g., Prometrium) is the preferred form, typically dosed at 100mg daily or 200mg for 12-14 days per month. Many women find 200mg nightly improves sleep and reduces anxiety. For women sensitive to oral progesterone (experiencing mood changes, excessive sedation, or bloating), vaginal administration can mitigate side effects. Progesterone-releasing IUDs (like Mirena) are excellent alternatives, providing endometrial protection and contraception, especially useful during the heavy and unpredictable bleeding of perimenopause. Duavee (an oral estrogen combined with bazedoxifene, a SERM) is another option for uterine protection without traditional progesterone.

Estradiol (E2): This is the primary estrogen replaced. Dr. Rubin generally prefers transdermal delivery (patches, gels, sprays) over oral estradiol. Transdermal routes bypass the first-pass metabolism in the liver, which reduces the risk of blood clots and avoids significantly increasing Sex Hormone-Binding Globulin (SHBG), thereby maintaining better levels of free testosterone and potentially improving sexual function. Patches are available in various doses (twice-weekly patches are often better tolerated than once-weekly). Gels and sprays are applied daily. Systemic estrogen rings (e.g., Femring) are another option, lasting for three months, though Dr. Rubin notes they can sometimes "peter out" before the three-month mark in her clinical experience. Oral estradiol is still a viable option for healthy, younger menopausal women without significant cardiovascular risk factors. Dosing is titrated based on symptoms and lab results (using sensitive LCMS assays for estradiol is crucial), with breast tenderness often being an indicator of excessive estrogen.

Testosterone: Dr. Rubin passionately argues for the importance of testosterone in women's health, affecting libido, mood, energy, cognitive function, muscle mass, and genitourinary health. Women naturally have significantly more testosterone than estradiol (when measured in normalized units). Testosterone decline is age-related, often beginning in a woman's 30s, and is not solely a menopausal event; birth control pills can also suppress ovarian testosterone production. While FDA-approved testosterone products for women are lacking in the U.S. (though available in Australia), Dr. Rubin uses off-label FDA-approved male topical testosterone gels (like Testim 1%) at approximately one-tenth of the male dose, applied to the calf. She advises that full effects may take 3-5 months. At appropriate doses, side effects like acne or increased leg hair growth are manageable, and virilizing effects (voice deepening, clitoromegaly) are rare unless super-physiologic doses (often seen with unregulated pellets) are used.

Genitourinary Syndrome of Menopause (GSM) and Local Therapy

Dr. Rubin highlights Genitourinary Syndrome of Menopause (GSM) as a severely underappreciated and undertreated condition. Previously known as "vulvovaginal atrophy," GSM encompasses a range of symptoms due to hormone deficiency in the vulva, vagina, and lower urinary tract, including vaginal dryness, pain with intercourse, itching, burning, urinary frequency, urgency, and a significantly increased risk of recurrent UTIs. She describes local vaginal hormone therapy as "better than Viagra for women," emphasizing its safety, efficacy, and affordability.

Low-dose vaginal estrogen (creams like Estrace, tablets like Vagifem, or local rings like Estring) or vaginal DHEA (Intrarosa) can reverse these changes by restoring the local hormonal environment, improving tissue health, and reducing UTI risk by over 50%. These local therapies do not carry the systemic risks associated with higher-dose systemic HRT and are considered safe even for women with a history of breast cancer or blood clots, under expert guidance. Dr. Rubin notes that even women on systemic HRT may still require local therapy for optimal GSM relief. She also discusses the vulvar vestibule, a highly hormone-sensitive area homologous to the male urethra, which is often the source of pain and UTI-like symptoms. For refractory cases, she compounds a topical cream containing 0.01% estradiol and 0.1% testosterone, which has shown miraculous results for pain in this region.

Dr. Rubin estimates that widespread use of local vaginal estrogen among Medicare-eligible women could save the healthcare system $6 to $22 billion annually by preventing UTIs and their complications. However, inappropriate FDA-boxed warnings on these products (mirroring those for systemic HRT) create significant barriers to their use.

Navigating Menopause Care: Challenges and Solutions

A central theme is the challenge women face in accessing knowledgeable menopause care. Dr. Rubin decries the lack of physician training and the pervasive misinformation stemming from the WHI fallout. She points to systemic biases, noting how the FDA and pharmaceutical industry have deprioritized women's health research and drug development (e.g., the higher bar for approving female testosterone compared to male testosterone).

For women seeking care, Dr. Rubin recommends resources like Menopause.org (The Menopause Society) and ISSWSH.org (International Society for the Study of Women's Sexual Health) to find practitioners. She cautions against exploitative practices, such as clinics that exclusively push expensive, unregulated compounded hormones (especially pellets, which can deliver super-physiologic and irreversible doses) or extensive, non-validated testing (like routine saliva tests).

Regarding the "timing hypothesis" (the idea that HRT should ideally be started within 10 years of menopause or before age 60 for optimal safety), Dr. Rubin suggests that while shared decision-making is key for later initiators, the data supporting strict cutoffs is questionable, especially with modern transdermal therapies. There is no evidence-based reason to arbitrarily stop HRT after a certain duration; benefits, particularly for bone health, are lost upon cessation.

For women with a family history of breast cancer, DCIS, or a personal history of treated breast cancer, decisions about HRT are complex and highly individualized, requiring thorough discussion of risks and benefits, often involving an oncologist as part of a multidisciplinary "pit crew." Dr. Rubin argues that the fear surrounding estrogen is often disproportionate, drawing parallels to how testosterone is managed in men with prostate cancer, where quality of life is a significant consideration.

Finally, Dr. Rubin passionately argues that menopause is not just a women's issue but an "everybody problem." She notes that men who are divorced, single, or widowed have significantly worse health outcomes, and since many divorces occur during the perimenopausal/menopausal years (ages 40-60), addressing women's menopausal health is crucial for maintaining partnerships and, by extension, men's longevity.

Conclusion

Dr. Rachel Rubin's conversation with Peter Attia provides a powerful and enlightening perspective on women's hormonal health. The core message is that menopause is a profound physiological transition with far-reaching health consequences that have been historically misunderstood and inadequately addressed, largely due to the misinterpreted legacy of the WHI study and systemic neglect within the medical establishment. Modern, individualized Hormone Replacement Therapy—encompassing estradiol, progesterone, and testosterone—offers significant benefits for symptom relief, long-term health, and overall quality of life, with risks that are often overstated when appropriate formulations and delivery methods are used. Furthermore, local vaginal hormone therapies represent a safe, effective, and underutilized tool for managing Genitourinary Syndrome of Menopause.

The episode underscores the urgent need for better physician education, increased research in women's health, and patient empowerment. By equipping women with accurate information and encouraging clinicians to become proficient in menopause management, the devastating impact of decades of insufficient care can be reversed, ultimately improving the health, well-being, and longevity of half the population and, by extension, their families and society as a whole.