Issue 163  /  September 11, 2026  /  Feature

Testosterone for Women Got a Market Before it Got Evidence

Testosterone prescribing to US women rose 58.7% last year with no product approved for them. As the FDA prepares to ask what is known about its safety, the history of one 3,656-woman trial shows that evidence in this category follows ownership rather than demand.

Testosterone for Women Got a Market Before it Got Evidence

In 2008, BioSante Pharmaceuticals began enrolling postmenopausal women with hypoactive sexual desire disorder, or HSDD, into a placebo-controlled trial of LibiGel, a daily testosterone gel.

Neither the women nor their doctors knew who was getting the real gel.

To qualify, a woman had to be 50 or older with at least two cardiovascular risk factors such as high blood pressure or diabetes. The design was published in the American Heart Journal in January 2012, with William White of the University of Connecticut as lead author and Michael Snabes, who led clinical work at BioSante, among the co-authors. It records a safety bar agreed with FDA in advance. LibiGel would count as safe if the trial could rule out testosterone more than doubling the risk of heart attacks, strokes and related events compared with placebo. Breast cancer was tracked as a second main outcome, and women were to be followed for up to five years.

The trial, known as BLISS, enrolled 3,656 women. An independent safety committee, which could see who was on testosterone while BioSante could not, reviewed the data nine times. At the last review, in September 2012, BioSante reported 53 confirmed cardiovascular events and 27 breast cancers, with rates it put at about 0.72% and 0.37%. Those figures are company-stated and combine the testosterone and placebo groups. The release did not say what the rates were calculated against, and the figures say nothing about testosterone compared with placebo.

BioSante concluded the trial in the same announcement.

It said average use had reached 24.5 months against FDA's 12-month minimum, that it had enough safety data to support an application for approval, and that stopping would bring significant savings. The committee had raised no safety issues, so the decision to stop was not a safety call.

Nine months earlier, the company's two efficacy trials in 1,172 women in surgical menopause had missed their main goals, which it attributed to a stronger than expected placebo response. It said at the time it planned new efficacy trials.

No journal has published the results. The company's press releases and a blinded interim summary presented at a 2011 scientific meeting combined the two groups.

Ido Avivi, Cynthia Stuenkel and colleagues at UC San Diego noted in JACC: Advances in May that BLISS was completed and never published after the efficacy trials failed. Once LibiGel stopped moving toward approval, no one had a commercial reason to publish it.

The efficacy trials have a gap of their own. Reviewers for Australia's Pharmaceutical Benefits Advisory Committee, assessing a different testosterone product at the committee's November 2025 meeting, noted that the two LibiGel efficacy trials appear only as abstracts. That kept them out of Islam and colleagues' 2019 meta-analysis in The Lancet Diabetes & Endocrinology, which the reviewers said may bias that analysis, since both trials found no benefit.

On September 17, FDA's Office of Women's Health and its Center for Drug Evaluation and Research hold a public workshop on testosterone use in menopausal women. The agency's notice lists the gaps it wants examined, among them the absence of long-term data on heart and breast cancer risk. Written comments are open until October 19 under docket FDA-2026-N-5479.

BLISS would not fill the long-term gap alone. Average use stopped near two years, about where the 2019 Global Consensus Position Statement on testosterone for women, led by Susan Davis and published in the Journal of Clinical Endocrinology & Metabolism, said existing safety data ends. What BLISS holds that the published record lacks is its population.

The consensus warned that the trials behind its safety findings excluded women at high risk of heart and metabolic disease. BLISS was built to study women with elevated cardiovascular risk.

Many of the women now getting prescriptions carry those risks. Using Epic's Cosmos database of more than 300 million patient records, the UC San Diego team found that testosterone prescribing to women held between 46 and 50 per 100,000 from 2016 to 2021, then rose to 130.8 per 100,000 in 2025. That was 90,482 prescriptions, up 58.7% from 2024. Women aged 45 to 64 accounted for 62.2% of them and were the fastest-growing group, up 79.1% in a year. Of the women prescribed it, 51.2% had high blood pressure, abnormal cholesterol or type 2 diabetes on record, about the same share as women in Cosmos who weren't prescribed it. HSDD was the diagnosis attached in 8.2% of cases. The authors caution that visit diagnosis codes may not reflect why a drug was prescribed, and Cosmos only sees prescribing inside health systems that use Epic.

The trial's commercial history runs through securities filings. BioSante merged with ANI Pharmaceuticals in June 2013. Just before the deal closed, BioSante gave its shareholders contingent value rights, a claim on part of any future LibiGel deal. Under the terms in its 2013 registration statement, holders would split 66% of the net cash from a sale or license of LibiGel completed within 10 years. ANI's annual report for 2023 says the rights expired in June 2023 with no payments made.

A safety trial like BLISS has one natural buyer, a company taking a product to approval. Without a product on that path, analyzing and publishing the data costs money and earns none back. The rest of the market has no reason to pay for it either. Every testosterone prescription written for a US woman today is off-label or compounded, since no product is approved for her, and neither channel requires a women's safety trial. The contingent value rights gave a LibiGel deal 10 years to happen. They paid nothing.

The next developers are building their own record. Aviva Bio said in January it had received formal FDA feedback on AVA-291, a modified testosterone designed to resist converting into estrogen in the body, and that the agency's feedback acknowledged the potential breast cancer risk of testosterone in women. The company says the molecule is covered by issued US patents running to at least 2041. That kind of protection is what makes a long safety trial worth funding.

It also shapes what the next trials will measure.

Evidence from a new molecule describes that molecule. The testosterone women are prescribed today, men's products used at a fraction of the dose or compounded versions, sits outside any company's path to approval for women, which gives it the weakest commercial case for a new outcomes trial.

In this category, safety evidence follows ownership. The testosterone women already take has no owner who needs it proven safe for them.

This article is for informational purposes and is not medical advice.

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Sources

— Keisha, Editor of The Luteal