Peter Attia MD348 ‒ Women’s sexual health, menopause, and hormone replacement therapy (HRT)
CHAPTERS
- 0:00 – 5:37
Rachel Rubin's Path from Urology to Women's Sexual Health
Peter Attia welcomes Rachel Rubin and asks how a urologist ended up in women's sexual health. Rubin describes urology as quality-of-life medicine and explains why she gravitated toward sexual medicine and women's care.
- •Urologists are board certified to care for everyone's genital and urinary tracts
- •Society has taught urologists more about men's sexual health than women's
- •Rubin chose urology over OBGYN because she likes quality-of-life work and long patient relationships
- •She now teaches colleagues to care for women's sexual health
- 5:37 – 14:27
The Gas Tank Analogy: Menopause and Perimenopause Hormone Chaos
Rubin uses a gas tank analogy to explain why menopause is an abrupt loss of hormones and why perimenopause is erratic. She gives estradiol numbers across the menstrual cycle, pregnancy and perimenopause, and she and Attia walk through the LH, FSH and progesterone cycle.
- •Menopause is described as a 'castration event' in which the tank is essentially empty
- •Normal estradiol runs about 50 to 150 across a cycle, versus 3,000 or more in pregnancy
- •Perimenopausal estradiol can swing from near zero to 1,000 and back
- •Symptoms can come from levels that are too low, too high, or fluctuating
- •Progesterone comes from the shell of the egg after ovulation, and its withdrawal triggers the shedding of the lining
- 14:27 – 17:10
Why Women Respond So Differently to Progesterone
Attia asks why women vary in their sensitivity to the progesterone drop and to progesterone itself. Rubin points to GABA receptors and says about a third of patients love micronized progesterone, a third barely notice it, and a third react badly.
- •Sensitivity may relate to GABA receptors and progesterone metabolites
- •About a third of patients love progesterone for sleep and anxiety
- •About a third notice nothing, and a third are very sensitive
- •No one can yet predict who will react badly
- •Rubin says women's health needs far more research
- 17:10 – 20:36
Health Risks for Postmenopausal Women Without Hormones
Attia asks what a woman in her 60s who has gone a decade without hormones stands to lose. Rubin reframes the question around the risks of not treating, covering genitourinary, bone, brain, heart and mood effects.
- •Rubin says the risk of not taking hormone therapy is rarely discussed
- •Loss of hormones raises the risk of recurrent UTIs and pelvic pain
- •Osteoporosis and hip fractures are a major risk, with fractures killing about as many women as breast cancer
- •Heart disease and dementia are higher in women, though Rubin says dementia data on hormones is unclear
- •Perimenopause may be harder on mental health than the later empty-tank state
- 20:36 – 30:51
The Women's Health Initiative: History and Misinterpretation
Attia recounts how HRT became standard care and why the NIH launched the WHI. Rubin and Attia explain how the study was announced, why it used a single synthetic regimen, and how the results were misread. They discuss the absolute risk of 0.1% and the findings that estrogen alone lowered breast cancer incidence and mortality.
- •HRT was standard in the 1960s through the 1990s, supported by epidemiology open to healthy-user bias
- •The WHI press conference caused use to crash overnight from about 40% of women
- •The study tested one synthetic estrogen-progestin regimen at one dose
- •Rubin cites decreases in colon cancer, fractures, diabetes and mortality, and no cardiovascular difference over time
- •The 24% relative increase in breast cancer incidence translated to about one extra case per 1,000 women, with no increase in breast cancer mortality
- 30:51 – 36:52
A Lost Generation of Women and Doctors Never Trained in Menopause
Rubin describes a conference with almost no menopause teaching, and Attia says he has focused on the generation of women deprived of HRT. They discuss how little menopause training doctors receive and how specialists across fields disclaim responsibility.
- •Rubin says a conference of 20,000 internists offered almost no menopause content
- •Doctors who prescribed hormones retired or died without training successors
- •Rubin says fewer than 6% of internal medicine, OBGYN and family practice doctors get even an hour of menopause education, and Attia says he learned zero
- •Endocrinologists and psychiatrists say prescribing hormones is not their field or not covered by malpractice insurance
- •Rubin argues menopause affects every organ system and is not niche medicine
- 36:52 – 48:53
Testosterone in Women: Role, Dosing and Side Effects
Attia introduces testosterone as the third hormone. Rubin explains it declines from the 30s, is overlooked in birth control and menopause care, and has global consensus support for low libido. She describes dosing with male topical products at much lower amounts, side effects, timelines and her views on pellets and Natesto.
- •Women have far more testosterone than estradiol when units are normalized
- •Having regular periods does not mean hormones are normal
- •Testosterone has receptors in the genitals and urinary tract
- •Rubin uses FDA-approved male gels at roughly a tenth of the dose, applied to the calf
- •She avoids pellets because of supraphysiologic levels and the inability to remove them
- •Benefits may take three to five months to be fully noticed
- 48:53 – 57:22
Why No FDA-Approved Female Testosterone and the Box Warning Problem
Attia asks why no female testosterone formulation exists, and Rubin says the FDA demanded another five years and a billion dollars. They contrast this with the quick removal of the testosterone box warning for men after the Traverse trial and the lingering estrogen warning.
- •Rubin says the FDA required five more years and another billion-dollar study because women have breast tissue
- •Companies abandoned the field after the goalposts moved
- •The men's testosterone box labeling was removed quickly after Traverse, while the estrogen box labeling remains
- •Rubin cites a humility problem in medicine and little funding or industry interest in women's health
- •Attia notes that other doctors used to scold him for prescribing hormones without engaging with the data
- 57:22 – 1:01:43
Fringe Hormone Clinics and the Vacuum Left by Mainstream Medicine
Attia raises the risk from 'doc in a box' hormone practices. Rubin says fringe clinics fill the gap left by mainstream medicine, and that fewer than 4% of women are on hormone therapy while there are too few knowledgeable prescribers.
- •Attia advises suspicion of doctors who sell hormones or run their own compounding pharmacies
- •Rubin says patients seek out whoever offers answers when mainstream doctors dismiss them
- •The same pattern shows up in men's health with testosterone pellet clinics
- •Rubin says fewer than 4% of women are on hormone therapy, worse than 10 years ago
- •Both agree every doctor who sees women of this age should be able to prescribe estrogen
- 1:01:43 – 1:10:21
The Progesterone Playbook: Dosing, Alternatives and Sequencing
Attia and Rubin compare how they prescribe progesterone, including doses, daily versus cyclic use, vaginal routes, progestin IUDs and Duavee. They also discuss endometrial surveillance and starting one hormone before the other.
- •Micronized progesterone is Rubin's first line, typically 100 mg daily or 200 mg cyclically
- •Attia often titrates to 200 mg if tolerated, noting improved sleep
- •For the 10 to 20% who react badly, options include vaginal progesterone, a progestin IUD, synthetic progestins or Duavee
- •Rubin does not do routine endometrial surveillance and relies on bleeding as a signal
- •Both like to stack therapies one at a time, usually starting with estradiol
- 1:10:21 – 1:17:29
Estradiol Basics: Biest, Compounding and 'What Are You Afraid Of?'
Attia introduces the three estrogens and asks about compounded Biest. Rubin and Attia explain why it arose after the WHI, why they avoid it, and how Rubin pushes clinicians to ask what they fear in a given patient.
- •Only estradiol has FDA-approved products, and Biest is an 80/20 estriol-estradiol compound
- •Biest grew out of the post-WHI underground and has no large-trial data
- •Rubin sometimes finds near-zero estradiol levels in patients on compounded creams
- •Attia once used Biest in a patient with breast cancer but based on a biochemical argument rather than human data
- •Rubin teaches clinicians to ask 'what are you afraid of?' and to weigh the risk of not acting
- 1:17:29 – 1:31:52
Systemic Estradiol Delivery: Oral, Sublingual, Patches, Gels and Rings
Rubin and Attia go through the toolbox for systemic estradiol. They cover oral and sublingual estrogen, patches, gels, sprays and the two FDA-approved vaginal rings, including the difference between systemic and local rings and why rings may wear off early.
- •Rubin starts most patients on transdermal estrogen because the KEEPS trial found better sexual function, due to effects on SHBG, though oral carries a slight clot increase
- •Oral estrogen is avoided in patients at clot risk, such as smokers or those with clotting predisposition
- •Sublingual estrogen is an unstudied possibility that avoids first-pass liver metabolism
- •Patches and gels each have trade-offs such as adhesion, allergy and drying time
- •Femring is a high-dose systemic ring and Estring is a low-dose local ring, and the two are easily confused
- •Rubin has seen rings lose effect in the final month, so levels can help with troubleshooting
- 1:31:52 – 1:39:56
Lab Testing: LC-MS Assays and Using Numbers with Symptoms
Attia and Rubin discuss how to test hormones without being misled. Both insist on sensitive LC-MS assays for estradiol and testosterone, and describe a middle path between never testing and over-testing, with symptoms first and numbers as a guide.
- •Non-LC-MS assays can be meaningless and biotin can interfere with them
- •Mainstream guidance says to treat symptoms only, while the fringe tests everything, including saliva
- •Rubin says levels help patients see why they feel bad and help troubleshoot
- •Attia uses FSH and estradiol together with symptoms and treats breast tenderness as a sign of too much estrogen
- •Both warn against overconfident social media claims of exact answers
- 1:39:56 – 1:46:29
The Wide-Ranging Symptoms of Menopause: Joints, Brain Fog and Mood
Rubin argues that menopause has the worst PR campaign because few recognize its full symptom range. She covers hot flashes, joint and musculoskeletal pain, and brain fog, citing Lisa Mosconi's work on rising brain estrogen receptor density, and ADHD-like symptoms in perimenopause.
- •Hormones act as a body-wide 'fluid' and their loss dries and inflames tissues
- •Hot flashes may be a vascular event and worse ones track with cardiovascular risk, according to Rubin
- •Joint pain, frozen shoulder and plantar fasciitis are part of what is called the musculoskeletal syndrome of menopause
- •Mosconi's early findings showed estrogen receptors in the brain upregulate rather than fall
- •Receptor fluctuation in perimenopause may explain new ADHD-like symptoms, and fog eases once levels stabilize
- 1:46:29 – 2:00:35
Genitourinary Syndrome of Menopause: UTIs, Vaginal Estrogen and Medicare Savings
Rubin traces the terminology from 'senile vagina' to GSM and explains why the urinary component matters. She describes how vaginal estrogen or DHEA can cut UTIs by more than half, the huge potential Medicare savings, the lingering box warning, and a personal story about her mother in the ICU.
- •The term changed to GSM in 2014, with a urology mentor fighting to include 'urinary'
- •Vaginal estrogen is safe for essentially everyone and costs about $13 a tube
- •Rubin says universal use among Medicare-eligible women could save $6 to $22 billion a year
- •Rubin calls vaginal hormones the original 'Viagra for women'
- •Her mother's ICU care showed how the box labeling blocks even this therapy
- •Systemic hormones often do not fully treat genitourinary symptoms, and Attia suggests a study on adding local estrogen
- 2:00:35 – 2:07:12
Vaginal DHEA, the Vulvar Vestibule and Compounded Testosterone for Pain
Rubin explains how vaginal DHEA works by converting into estrogen and androgens, and why it matters for hormone-sensitive tissues. She then covers anatomy of the vulvar vestibule and the one compounded combination she uses for persistent pain.
- •Vaginal DHEA (Intrarosa) is FDA approved and showed UTI reduction similar to estrogen in a recent publication
- •Genital and bladder tissues have androgen receptors, so estrogen alone may not suffice
- •The vulvar vestibule is rich in hormone receptors and rarely taught or examined
- •Persistent pain with sex can arise there despite systemic therapy
- •Rubin compounds 0.01% estradiol and 0.1% testosterone for the vestibule
- 2:07:12 – 2:11:13
Is It Too Late, and Should HRT Stop After 10 Years?
Attia poses two contentious questions: whether starting after menopause is too late and whether women should stop after 10 years. Rubin says the timing hypothesis is under question, lists the three indications for therapy, and argues there is no data supporting a stopping point.
- •Rubin says the timing hypothesis is questioned, citing Susan Davis, and favors shared decision-making
- •HRT is indicated for vasomotor symptoms, osteoporosis prevention and GSM
- •Local vaginal estrogen or DHEA is suitable at any age and throughout life
- •There is no data supporting stopping at ten years, and stopping loses bone gains
- •Rubin sees active cancer targeted by hormone therapy as the main reason to stop
- 2:11:13 – 2:17:40
Hormones, Breast Cancer Risk and Choosing Your Care Team
Attia asks how to manage hormones in women with BRCA mutations, DCIS or a history of breast cancer. Rubin draws a parallel with testosterone in prostate cancer, argues for shared decision-making, and uses a pit crew analogy for patients' care teams.
- •Surgical menopause in BRCA carriers without hormones trades breast cancer risk for bone and cardiovascular risk
- •Rubin sees no reason to withhold hormones after DCIS surgery if no endocrine therapy is planned
- •She cites emerging questioning for active breast cancer and compares it to the prostate cancer saturation model
- •Women should treat doctors as advisers and assemble a 'pit crew' of specialists
- •Rubin wants every woman offered the menu of options, not pushed into HRT
- 2:17:40 – 2:24:37
Finding Good Providers and Spotting Red Flags
Attia asks how women can find good practitioners and avoid exploitative ones. Rubin recommends reading widely, using menopause.org and ISSWSH.org, and lists red flags such as expensive compounded products, saliva testing and pellets. The episode closes with Rubin's argument that menopause medicine affects men's longevity.
- •Rubin sees danger both in dismissive doctors and in expensive pellet clinics
- •She recommends several menopause books and following a range of voices rather than one
- •menopause.org and ISSWSH.org help locate providers
- •Red flags include doctors offering nothing, or costly compounded products and saliva labs
- •Rubin closes with the claim that divorce during menopause years harms men's health
