Estrogen, Progesterone, and Testosterone: The Science of Hormones, Sexual Function, and Menopause

Dr. Rowan and host Haver detail the current off-label approach that has evolved out of necessity because no FDA-approved female testosterone product exists. The libido benefit in randomized trials was seen in about 50% of women, but the LibiGel trial failed due to a massive placebo effect. Dosing is challenging because approved products are designed for men who have 10–20 times higher levels. Rowan prescribes tubes with syringe drawing to measure a fraction, and she explicitly warns against packets. The host started prescribing testosterone only 3.5 years ago after learning from ISHWISH colleagues, and she now uses the pump on herself. They both avoid pellets because absorption is erratic, leading to levels often >100 ng/dL, which in a natural state would prompt a tumor workup. They cite transgender safety data showing high testosterone levels in trans men are not associated with increased breast cancer, but emphasize that such supraphysiologic levels are not the goal of menopausal medicine. The protocol embodies a harm-reduction, patient-led approach: aim for physiologic restoration, monitor levels, and be transparent that it’s therapy, not replacement.

Dr. Rowan points out that the earliest perimenopause symptoms are often overlooked because they involve sleep and mood, not hot flashes. She finds that progesterone-only therapy can be very effective in this phase, particularly for women with a strong history of cyclical mood symptoms. The key is proper administration: oral progesterone requires food for optimal absorption, and taking it without a meal reduces efficacy. Many women are told to take it before bed but after a long gap since dinner, which undermines results. If the patient becomes too sleepy the next day, Rowan recommends vaginal insertion of the same micronized tablet; this bypasses liver conversion to allopregnanolone, preserving the calming effect without excessive sedation. The host supports this protocol and has seen both benefits and paradoxical reactions, confirming it’s an individualized tool.

The host’s epiphany about poor transdermal absorption led her to routinely check estradiol levels in non-responders, which she now recommends at a 3-month point. Dr. Rowan builds on this by noting that she always obtains a baseline testosterone before starting therapy and rechecks at 6 weeks; she has seen ‘super absorbers’ reach high levels on tiny doses and has to reduce them. She also explains that the widely quoted normal ranges for testosterone are based on old, inaccurate assays that overestimated levels, so clinicians must understand lab methodology. The message is that hormone therapy should be guided by symptom response, but laboratory data can unlock stubborn cases and prevent harm.

Dr. Rowan describes a recent patient whom she ‘cured’ of sexual pain after years of ineffective pelvic floor PT. The woman had been on a contraceptive with an anti-androgenic progestin. Rowan switched her to a different method and prescribed compounded vulvar estrogen plus testosterone, leading to resolution. She emphasizes that many clinicians don’t link long-term pill use to vulvar pain, and that a smart pelvic floor PT often recognizes the hormonal component. The host is struck by this connection and the power of local hormone repair. This protocol exists at the intersection of sexual medicine and vulvovaginal dermatology, and highlights that often both estradiol and testosterone are needed.

Dr. Rowan explains that ethinyl estradiol potently stimulates the liver to produce clotting factors, raising thrombosis risk, and also increases SHBG, lowering free testosterone. This potency is why it stabilizes the uterine lining and suppresses ovulation so effectively. However, it is not the same as natural estradiol; the ethinyl modification makes the molecule stick to the receptor far longer and stronger. This insight directly impacts counseling: women on contraceptives who fear blood clots should know the risk is molecule-specific, not inherent to all estrogens. Host Haver shares that she had examined thousands of contraceptive packets and always presumed the ethinyl group fell off, and her residency faculty never corrected this. Dr. Rowan emphasizes that this misunderstanding fuels anti-hormone sentiment, but modern contraception is safe when prescribed appropriately, and the nuance can help women make informed choices. The conversation highlights how even seasoned OB/GYNs can have gaps in basic endocrine pharmacology.

Dr. Rowan details that natural progesterone has only one receptor, but progestins, being synthetic, can bind multiple receptors. Drospirenone is anti-androgenic and used for acne but can lower libido. Norethindrone acetate and medioxyprogesterone acetate (Provera) differ: norethindrone actually metabolizes into ethinyl estradiol, explaining its use in add-back therapy with Lupron to reduce hot flashes and bone loss, and its potentially different breast safety profile. Provera is glucocorticoid-active, leading to bloating and, in the WHI, increased cardiovascular risk. The host is stunned to learn that norethindrone can convert to ethinyl estradiol, as she never questioned why add-back uses a progestin for estrogen-like effects. Dr. Rowan also notes that many progestins interconvert (e.g., levonorgestrel metabolites are common). This knowledge allows clinicians to select progestins based on receptor profiles rather than simple trial and error. The segment challenges the ‘pick a pill, any pill’ mantra and redefines progestins as a pharmacologically diverse class.

Dr. Rowan emphasizes that testosterone levels are low for years before the final menstrual period; there is no cliff. She clarifies that while testosterone can improve libido and possibly other symptoms, it is not a replacement like estradiol but a pharmacologic therapy. The host agrees and adds that this nuance is critical because many women are told they are now ‘deficient.’ Rowan also notes that supraphysiologic testosterone (from pellets or high-dose injections) is akin to a performance-enhancing drug; some women may feel fantastic, but that lies outside physiologic menopause management. She draws on transgender medicine where individuals maintain much higher testosterone levels, but that is not the goal for cisgender menopausal women. The host mentions that she checks levels to avoid dangerous supraphysiologic dosing. The segment urges honesty about what evidence supports and reframes testosterone as a targeted intervention, not a blanket deficiency correction.

Dr. Rowan recounts that LibiGel produced an average of four more satisfying sexual events per month—an effect comparable to Viagra. However, the placebo group experienced an identical increase. The company went bankrupt, and no women’s product has since been approved. She attributes this to the powerful placebo effect: being enrolled in a study, receiving attention, and being given permission to address desire. Host Mary Claire Haver draws a parallel to Viagra, which was fast-tracked with just six months of safety data and had deaths in trials, while women needed to prove no breast cancer risk. The story exposes a glaring gender gap in regulatory standards and how the very context of care can swamp drug effects. Both experts lament that women now must use off-label men’s products and that the medical system has left them without an FDA-approved option for decades.

Host Haver shares a vivid story of a patient who put an entire box of patches on her body and still had postmenopausal estradiol levels, which was her epiphany that absorption varies dramatically. Dr. Rowan confirms she sees this often and will check estradiol if a patient doesn’t respond. She explains that the vagina is the most absorbent surface for systemic hormone delivery, though typical vaginal estrogen products for GSM are dosed only for local effect. If a woman truly needs systemic hormone and doesn’t absorb transdermally, oral estrogen or high-dose vaginal administration can be used. They clarify that the phrase ‘vaginal estrogen treats only the vagina’ applies to low-dose FDA-approved creams and rings; higher doses can achieve systemic levels, just as progesterone vaginal suppositories are used in fertility treatment. This nuanced discussion empowers clinicians to escape the ‘one route fits all’ mentality and personalize hormone therapy based on measured response.