The Federal Register (FR) notice (here) appearing on today’s pre-publication page describes the long and tedious process of finalizing one of the last remaining Drug Efficacy Study Implementation (DESI) notices, and ends with a final FDA decision that there is a lack of substantial evidence of efficacy for the use of certain estrogen-androgen fixed combination drug products. The notice cites the products as “Syntest D.S. (1.25 milligrams (mg) esterified estrogens/2.5 mg methyltestosterone) and Syntest H.S. (0.625 mg esterified estrogens/1.25 mg methyltestosterone), both labeled for use in treating moderate to severe vasomotor symptoms associated with the menopause in patients not improved by estrogen alone.”

Based on the FDA’s June 13, 2003 hearing request, two companies requested hearings: Syntho Pharmaceuticals, Inc. (Syntho), 230 Sherwood Avenue, Farmingdale, New York 11735, and Solvay Pharmaceuticals, which was acquired in 2010 by Abbott Laboratories, 100 Abbott Park Road, Abbott Park, Illinois 60064. At the time of Solvay’s 2003 hearing request, the firm marketed Estratest and Estratest H.S. On January 31, 2011, the FDA sent a letter to Abbott asking whether it wanted to pursue the hearing request regarding the two Estratest products. On June 21, 2011, Abbott responded by withdrawing the hearing request that had been filed by Solvay Pharmaceuticals before its acquisition by Abbott.

After requesting a hearing on the DESI product on May 14, 2003 and submitting data in support of its hearing request on June 13, 2003, and after repeated requests from the FDA (dated January 31, 2011 and June 18, 2025) regarding whether it still wanted to pursue its request for a hearing, Syntho apparently threw in the towel. On August 1, 2025, the company stated, in a response to the FDA, that it had decided to withdraw its hearing request.

When Syntho finally agreed to withdrawal its hearing request, all remaining hearing requests on all estrogen-androgen fixed combination drug products subject to the hearing requests were considered resolved. The FDA, therefore, affirms that “such products lack substantial evidence of effectiveness for the treatment of moderate to severe vasomotor symptoms associated with the menopause in patients not improved by estrogen alone,” and these products can no longer be legally marketed.

The story may seem straightforward, but it has taken 50+ years to resolve this DESI action and finally come to a conclusion. However, I can tell you that, when I was at the FDA, trying to explain why the Agency would not accept ANDAs for these marketed DESI products was always a bit of a tightrope walk. And, after leaving the Agency and working as an expert FDA consultant, explaining to clients why two firms were able to market the products and others were not, and, again, explaining why the FDA would not accept ANDAs for the two combination products was also a bit of a slippery slope. However, this age-old pending DESI review is now finally resolved and no more explanations are needed except, perhaps, for this postmortem. The runway was long, but now the plane has finally landed.

The FDA says, “Firms must notify the Agency of certain product discontinuations in writing under section 506C(a) of the FD&C Act (21 U.S.C. 356c). Some firms may have previously discontinued manufacturing or distributing products covered by this notice without discontinuing the listing as required under section 510(j) of the FD&C Act (21 U.S.C. 360(j)). Other firms may discontinue manufacturing or distributing listed products in response to this notice. All firms are required to electronically update the listing of their products under 510(j) of the FD&C Act to reflect discontinuation of unapproved products covered by this notice (21 CFR 207.57(b)). Questions on electronic drug listing updates should be sent to eDRLS@fda.hhs.gov.” Thus, any enforcement discretion will be over as of the effective date of the notice, which is set to be thirty days after its publication in the FR on May 27, 2026.