Application Sites and Blood Levels in Men
As prescribers of testosterone for men and women we have followed blood levels for many years and have some insight. However, we know some vary their application site, some go for testing hours after application and depending on application technique and site some patients may be getting considerable variation in their levels from day to day. If a male uses testosterone the levels should remain pretty stable for 24-48 hours. But by day 5 levels would return to normal if stopped.
Most of the dosing schedules and blood levels studies come from those using FDA-approved testosterone formulations in men, application sites vary by product and significantly affect absorption:
– Testosterone gel 1% is applied to shoulders, upper arms, and/or abdomen (not to genitals, chest, armpits, knees, or back), with steady-state serum concentrations achieved by approximately 14 days.
– Testosterone topical solution is applied to the axilla, achieving physiologic testosterone concentrations (300-1050 ng/dL the nl range for men) with steady-state by approximately 14 days.
– Testosterone gel (thigh application) is applied to the thighs, with dosing adjusted based on serum testosterone measured 2 hours post-application.
Arms demonstrate superior testosterone absorption compared to legs. Based on studies comparing different application sites, the rank order of optimal absorption of bioavailable testosterone is shoulder>arm> back > thigh > abdomen > chest > shin. When specifically comparing arms versus legs, the upper arm achieved significantly higher testosterone absorption than the thigh, which in turn exceeded absorption from the shin (lower leg) and no studies have looked at the back of the knee for men. Abdominal application has 30-40% lower available testosterone. Most package inserts will tell you not to use the legs.
Application Sites and Blood Levels in Women
No FDA-approved testosterone formulation exists for women in the United States. so no official recommendation from male products is claimed. However, transdermal testosterone has been studied off-label:
– Transdermal testosterone 1% cream (0.5-1 mL applied topically once daily) is approved in Australia for postmenopausal women with hypoactive sexual desire dysfunction. In a study of healthy women receiving 10 mg daily testosterone cream, median serum testosterone increased 5.0-fold. When axillary testosterone solution was applied to healthy premenopausal women, washing the application site at 2 or 6 hours decreased testosterone exposure (AUC) by up to 35%. In menopausal women skin would be thinner and levels may be much hire and yet susceptible to washing greater.
Estrogen gel application has not been shown to interfere with testosterone levels. And for sexual function some studies show the most improvement with combined dosing. Some women are not eligible for estrogen and can find successful therapy with testosterone alone.
Safety Considerations
Secondary exposure risk is a critical safety concern, particularly for women and children. When male partners applied testosterone gel to upper arms/abdomen, all unprotected female partners showed serum testosterone >2 times baseline during skin-to-skin contact; covering the application site with a shirt completely prevented transfer. I have had a case where the levels went into normal male levels just from that proximity.
Adverse effects in women receiving transdermal testosterone include hirsutism, acne, virilization (voice deepening, clitoral enlargement), and weight gain, with some effects potentially irreversible, The American College of Obstetricians and Gynecologists notes that transdermal testosterone can be considered for short-term use (up to 6 months) in postmenopausal women with sexual interest disorders, but long-term safety data are lacking.
Adverse effects in men include application site irritation (7-8%), increased hematocrit (4-7%), headache (5-6%), and elevated PSA. Polycythemia with high red blood cell counts may require dose reduction or discontinuation.
References
- Testosterone. Food and Drug Administration. Updated date: 2024-12-01.
- Testosterone. Food and Drug Administration. Updated date: 2025-03-01.
- Testosterone. Food and Drug Administration. Updated date: 2025-08-01.
- Compounded Bioidentical Menopausal Hormone Therapy: ACOG Clinical Consensus No. 6. Obstetrics and Gynecology. 2023;142(5):1266-1273. doi:10.1097/AOG.0000000000005395.
- Female Sexual Dysfunction: ACOG Practice Bulletin Clinical Management Guidelines for Obstetrician-Gynecologists, Number 213. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Obstetrics and Gynecology. 2019;134(1):e1-e18. doi:10.1097/AOG.0000000000003324.
- Sexual Dysfunction in Women. Davis SR. The New England Journal of Medicine. 2024;391(8):736-745. doi:10.1056/NEJMcp2313307.
- Disposition of Urinary and Serum Steroid Metabolites in Response to Testosterone Administration in Healthy Women. Elings Knutsson J, Andersson A, Baekken LV, et al. The Journal of Clinical Endocrinology and Metabolism. 2021;106(3):697-707. doi:10.1210/clinem/dgaa904.
- Efficacy and Safety of Transdermal Testosterone in Postmenopausal Women With Hypoactive Sexual Desire Disorder: A Systematic Review and Meta-Analysis. Achilli C, Pundir J, Ramanathan P, et al. Fertility and Sterility. 2017;107(2):475-482.e15. doi:10.1016/j.fertnstert.2016.10.028.
