348 ‒ Women’s sexual health, menopause, and hormone replacement therapy (HRT)

KEYPOINTS

• 01

  Menopause is an empty gas tank, and perimenopause is the chaos before it

  Rubin calls menopause a 'castration event'. Around 52 the ovaries largely stop making estrogen, progesterone and testosterone, while men's levels fall slowly. In a typical cycle estradiol runs from about 50 pg/mL at the low point to about 150 at ovulation (pregnancy is 3,000+). In perimenopause it can swing from 200 to 900 within ten days and then drop to zero, because the brain's FSH pushes a dwindling egg supply to overshoot.

• 02

  Women vary widely in how they respond to progesterone

  Rubin suspects GABA-receptor effects; nobody can predict it. When she gives micronized progesterone, about a third of patients love it (better sleep, less anxiety), a third notice nothing, and a third are sensitive (sleepy, bloated, or worse). Peter puts the bad-reaction group at 10–20%.

• 03

  Going without hormones carries real risks too

  Rubin says doctors talk about the risks of medication but rarely about the risks of not taking it. Without hormones, the genital and urinary tissue loses its acidity and protective bacteria, and UTIs rise sharply. Osteoporosis follows: about as many women die from hip fractures as from breast cancer, and Peter adds that half of survivors never regain their previous function. She adds heart disease and dementia, admitting the brain data is weak.

• 04

  The WHI scare came from a press conference and relative risk

  The billion-dollar trial tested one old regimen at one dose (equine estrogen, plus medroxyprogesterone with a uterus). Results were announced at a press conference before the paper came out, and hormone use fell from roughly 40% of women to almost nothing. The headline was a 24% relative rise in breast-cancer incidence in the combined arm, with no rise in breast-cancer deaths. Peter says the absolute increase was about 0.1%, roughly one extra diagnosis per 1,000 women, and calls it the greatest injustice of modern medicine in his lifetime. Unreported: fewer fractures, colon cancers and diabetes cases, lower overall mortality, and lower breast-cancer incidence and death with estrogen alone.

• 05

  A generation of doctors never learned to prescribe hormones

  Fewer than 6% of internists, OB-GYNs and family doctors get even an hour of menopause training. Fewer than 4% of eligible women now use hormone therapy, which is worse than ten years ago. Rubin works out about 84 million US women over 40 and about 3,000 clinicians listed on the Menopause Society site.

• 06

  Women's testosterone falls with age, not at menopause

  The decline starts in the 30s. Testosterone receptors are found in the genitals, urethra and bladder, so low levels affect more than libido. There is global consensus that it treats low libido after menopause, but the US has no FDA-approved female product (Australia has one). Rubin says the FDA demanded a second five-year study after the first showed safety, and companies quit.

• 07

  Rubin's playbook adds one hormone at a time

  Both doctors usually start with transdermal estradiol, because hot flashes are the most pressing symptom and stacking shows what each drug does. Then comes progesterone: 100 mg oral micronized nightly, or 200 mg for 12–14 days a month, with Peter often going up to 200 if tolerated. Taking it vaginally can reduce sedation. Testosterone is added last. Rubin uses about a tenth of a male dose: roughly 0.5 mL of 1% gel on the calf daily, with a 5 mL tube lasting about 7–10 days. She avoids pellets: supraphysiologic and irreversible.

• 08

  Oral, patch, gel and ring estrogen each have trade-offs

  Oral estrogen passes through the liver, raises clotting proteins and SHBG, and so is avoided in smokers, people with obesity, or anyone at clotting risk. The KEEPS trial found transdermal estrogen better for sexual function. Patches can fail with sauna use or heavy sweat. The Femring (0.05/0.1) is systemic and needs progesterone. The 2 mg Estring is local only. Pharmacists sometimes mix them up, and Rubin often sees levels fade in a ring's third month.

• 09

  Use labs as a guide, but trust symptoms most

  Both insist on sensitive LC-MS assays for estradiol and testosterone. Peter warns that ELISA tests can be thrown off by biotin and other interference, and the better test costs maybe $5–10 more. Symptoms come first. An FSH of 78 with estradiol of 40 nudges Peter to raise the dose, and breast tenderness is his clearest sign of too much.

• 10

  Local vaginal hormones are safe and cut UTIs by more than half

  Estradiol cream (about $13 a tube), the Estring, or vaginal DHEA (Intrarosa) treats genitourinary syndrome of menopause: dryness, painful sex, urgency, leakage and UTIs. Rubin says these are safe at any age, including after blood clots or breast cancer, and don't raise blood estradiol, so women on systemic therapy can add them. Her group estimates that if Medicare patients used vaginal estrogen, Medicare would save $6–22 billion a year. Yet they still carry the systemic-estrogen boxed warning.

• 11

  Neither age nor ten years of use is a reason to stop

  Rubin says the timing hypothesis rests on the WHI's old drugs, and Susan Davis has recently questioned even that. She calls osteoporosis prevention 'a green light' for offering therapy at any age. She sees no evidence for stopping after ten years. Bone gains disappear quickly when hormones stop, and stopping may destabilize plaque. The one reason she accepts is an active cancer being treated by blocking hormones.