Testosterone physiology in women and the long road to approval

Sharon J. Parish, MD, IF, NCMP, describes the Intrinsa patch, developed by Procter & Gamble, which delivered 300 micrograms of testosterone, the dose thought to reflect physiologic levels during women's reproductive years. She pauses to review testosterone physiology. Women's peak levels, roughly one-tenth those of young men, occur between about ages 18 and 30, and they begin declining in the late 30s and early 40s to about half of those levels.

She explains that androgens come from both the adrenal glands and the ovaries, and that ovarian decline begins even before perimenopause. Brain receptors that drive desire see less testosterone, and lower levels likely reach the genitalia as well. Replacement, she emphasizes, aims to restore women to that physiologic range, never above it.

The patch was first studied in surgically menopausal women taking estrogen. Subsequent randomized trials, 6 to 8 depending on which are counted, included naturally menopausal women both on and off estrogen. Across these 24-week trials, the patch improved sexual desire, the primary end point, along with other domains of sexual function. However, Parish says the FDA required longer-term randomized safety data for breast, uterine, and cardiovascular outcomes. The patch was approved in Europe but never in the United States, and it was later withdrawn for commercial rather than medical reasons.

Parish then describes LibiGel, a gel studied in women at elevated cardiovascular risk that showed no adverse safety signal but did not meet its efficacy thresholds. She also reviews a government-approved 1% testosterone cream in Australia formulated to deliver the patch's physiologic dose. US patients can obtain it through a non-US distributor, and she encourages use of a telemedicine provider because testosterone remains a controlled substance. Dorr notes that its concentration mirrors many compounded preparations.

In the next episode, Parish explains how a meta-analysis and global consensus statement reshaped the evidence base, and why the push toward higher doses has outpaced the data.