Notice2026-10479
Drugs for Human Use; Drug Efficacy Study Implementation: Estrogen-Androgen Fixed-Combination Drug Products; Syntest D.S. and Syntest H.S. Tablets; Withdrawal of Hearing Requests; Final Resolution of Drug Efficacy Study Implementation 7661
Primary source
Metadata and text below are from the Federal Register, a public-domain U.S. government work. Always verify the official published version before relying on it for any legal matter.
Published
May 27, 2026
Effective
June 26, 2026
Issuing agencies
Health and Human Services DepartmentFood and Drug Administration
Abstract
The Food and Drug Administration (FDA or Agency) is announcing that all outstanding hearing requests for estrogen-androgen fixed- combination drug products under Docket FDA-1998-P-0083 (formerly 76N- 0377) (DESI 7661) have been withdrawn. Therefore, as proposed in the April 14, 2003, notice of opportunity for hearing (NOOH), FDA finds that the products subject to this proceeding have not been shown to be effective for use under the conditions of use prescribed, recommended, or suggested in the labeling. Shipment in interstate commerce of any product identified in this docket (DESI 7661), or any identical, related, or similar (IRS) product, that is not the subject of an approved new drug application (NDA) or abbreviated new drug application (ANDA) is unlawful as of the date of this notice.
Full Text
<html>
<head>
<title>Federal Register, Volume 91 Issue 101 (Wednesday, May 27, 2026)</title>
</head>
<body><pre>
[Federal Register Volume 91, Number 101 (Wednesday, May 27, 2026)]
[Notices]
[Pages 31462-31464]
From the Federal Register Online via the Government Publishing Office [<a href="http://www.gpo.gov">www.gpo.gov</a>]
[FR Doc No: 2026-10479]
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
[Docket No. FDA-1998-P-0083 (formerly 76N-0377); DESI 7661]
Drugs for Human Use; Drug Efficacy Study Implementation:
Estrogen-Androgen Fixed-Combination Drug Products; Syntest D.S. and
Syntest H.S. Tablets; Withdrawal of Hearing Requests; Final Resolution
of Drug Efficacy Study Implementation 7661
AGENCY: Food and Drug Administration, Health and Human Services (HHS).
ACTION: Notice.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA or Agency) is announcing
that all outstanding hearing requests for estrogen-androgen fixed-
combination drug products under Docket FDA-1998-P-0083 (formerly 76N-
0377) (DESI 7661) have been withdrawn. Therefore, as proposed in the
April 14, 2003, notice of opportunity for hearing (NOOH), FDA finds
that the products subject to this proceeding have not been shown to be
effective for use under the conditions of use prescribed, recommended,
or suggested in the labeling. Shipment in interstate commerce of any
product identified in this docket (DESI 7661), or any identical,
related, or similar (IRS) product, that is not the subject of an
approved new drug application (NDA) or abbreviated new drug application
(ANDA) is unlawful as of the date of this notice.
DATES: This notice is effective June 26, 2026.
ADDRESSES: For access to the docket to read background documents or the
electronic and written/paper comments received, go to <a href="https://www.regulations.gov">https://www.regulations.gov</a> and insert the docket number, found in brackets in
the heading of this document, into the ``Search'' box and follow the
prompts and/or go to the Dockets Management Staff, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852, 240-402-7500 between 9 a.m. and 4 p.m.,
Monday through Friday. Publicly available submissions may be seen in
the docket.
The most relevant background documents regarding this matter are
available in the docket. However, additional background documents are
available upon request (see FOR FURTHER INFORMATION CONTACT).
FOR FURTHER INFORMATION CONTACT: Amber McKinley, Center for Drug
Evaluation and Research, Food and Drug Administration, 10903 New
Hampshire Ave., Bldg. 51, Rm. 5172, Silver Spring, MD 20993-0002, 301-
[[Page 31463]]
796-0061, email: <a href="/cdn-cgi/l/email-protection#5a1b37383f28741739113334363f231a3c3e3b74323229743d352c"><span class="__cf_email__" data-cfemail="9cddf1fef9eeb2d1ffd7f5f2f0f9e5dcfaf8fdb2f4f4efb2fbf3ea">[email protected]</span></a>.
SUPPLEMENTARY INFORMATION:
I. Background
In 1962, Congress amended the Federal Food, Drug, and Cosmetic Act
(FD&C Act) to require that ``new drugs'' (21 U.S.C. 321(p)) be proven
effective for their labeled indications, as well as safe, in order to
obtain FDA approval (Drug Amendments of 1962 (Pub. L. 87-781)). These
amendments also required FDA to conduct a retrospective evaluation of
the effectiveness of the drug products that FDA had approved as safe
between 1938 and 1962. FDA contracted with the National Academy of
Sciences/National Research Council (NAS/NRC) to make an initial
evaluation of the effectiveness of over 3,400 products that had been
approved only for safety between 1938 and 1962. The NAS/NRC reports for
these drug products were submitted to FDA in the late 1960s and early
1970s. The Agency reviewed and reevaluated the reports and published
its findings in Federal Register notices. FDA's administrative
implementation of the NAS/NRC reports was called the Drug Efficacy
Study Implementation (DESI). DESI covered the approximately 3,400
products specifically reviewed by the NAS/NRC, as well as the even
larger number of products that were IRS (see 21 CFR 310.6(b)(1)) to the
approved drug products and that had entered the market without FDA
approval. All drugs covered by the DESI review are ``new drugs'' under
the FD&C Act.
II. Final Resolution of Hearing Request Regarding Estrogen-Androgen
Fixed-Combination Drug Products Under Docket FDA-1998-P-0083 (Formerly
76N-0377); DESI 7661
In a Federal Register notice published on September 8, 1972 (37 FR
18225), FDA announced its evaluation of reports received from the NAS/
NRC under DESI 7661 regarding five fixed-combination drug products
containing an estrogen and an androgen. FDA stated in that notice that
it found these drugs to be effective ``for the prevention of postpartum
breast engorgement'' and ``for the menopausal syndrome in those
patients not improved by estrogen alone.'' With respect to the first
indication, on December 17, 1998, FDA withdrew approval of estrogen-
containing drug products insofar as they were indicated for postpartum
breast engorgement, because estrogens were not shown to be safe for
this use (63 FR 69631).\1\ Given FDA's findings in the December 17,
1998, Federal Register notice, the remainder of this notice focuses on
the second indication in the September 1972 notice, i.e. ``for the
menopausal syndrome in those patients not improved by estrogen alone.''
---------------------------------------------------------------------------
\1\ For additional background information leading to the 1998
Federal Register notice, see 68 FR 17953 (April 14, 2003).
---------------------------------------------------------------------------
In the Federal Register of September 29, 1976 (41 FR 43112), FDA
announced that the menopausal indication for fixed-combination drugs
containing an estrogen and an androgen (including the five drug
products identified in the September 8, 1972, notice) was revised to
read:
Moderate to severe vasomotor symptoms associated with the menopause
in those patients not improved by estrogen alone (There is no evidence
that estrogens are effective for nervous symptoms or depression which
might occur during menopause, and they should not be used to treat
these conditions).
Id. at 43113.
In 1981, in response to requests from the sponsors, FDA determined
that the effectiveness finding in the September 29, 1976, notice could
be applied to two fixed-combination drug products that were not listed
in the 1976 notice but were being marketed at the time: (1) conjugated
estrogens and methyltestosterone, and (2) esterified estrogens and
methyltestosterone. See 68 FR 17953, 17954 (April 14, 2003).
FDA took a renewed interest in both the safety and efficacy of
estrogen-androgen products while reviewing potential new safety
concerns about the products. As detailed in the Federal Register on
April 14, 2003 (68 FR 17953), an Agency review of the literature led
FDA to reclassify the September 1976 effectiveness finding for
estrogen-androgen fixed combination drug products to lacking
substantial evidence of effectiveness for the treatment of moderate to
severe vasomotor symptoms associated with menopause in patients not
improved by estrogen alone. At the same time, FDA also issued a Notice
of Opportunity for a Hearing (NOOH) to manufacturers and distributors
of drug products affected by the notice, regarding FDA's determination
that such products lacked substantial evidence of effectiveness for the
treatment of moderate to severe vasomotor symptoms associated with
menopause in patients not improved by estrogen alone. In response to
the April 14, 2003, NOOH, two companies requested hearings: Syntho
Pharmaceutical, Inc. (Syntho), 230 Sherwood Ave, Farmingdale, NY 11735,
and Solvay Pharmaceuticals, since acquired by Abbott Laboratories, 100
Abbott Park Rd., Abbott Park, IL 60064.
In response to the 2003 NOOH, Syntho filed a written notice of
participation and request for a hearing on May 14, 2003, and submitted
data in support of its hearing request on June 13, 2003. Syntho
marketed 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. In a letter dated January 31, 2011, FDA
asked Syntho whether it was interested in pursuing its hearing request.
Syntho affirmed its hearing request on March 1, 2011. By letter dated
June 18, 2025, FDA again asked Syntho whether it wanted to pursue its
hearing request regarding its Syntest D.S. and Syntest H.S. products.
By letter dated August 1, 2025, Syntho stated that it had decided to
withdraw its hearing request.
At the time of Solvay's 2003 hearing request, the firm marketed
Estratest and Estratest HS. On January 31, 2011, FDA sent a letter to
Abbott asking whether it wanted to pursue the hearing request regarding
its Estratest and Estratest HS products. On June 21, 2011, Abbott
responded by withdrawing the hearing request previously filed by Solvay
Pharmaceuticals before its acquisition by Abbott.
III. Conclusions and Order
There are no outstanding hearing requests regarding estrogen-
androgen fixed-combination drug products under Docket FDA-1998-P-0083,
DESI 7661. As proposed in the April 14, 2003, NOOH, 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. Shipment in interstate commerce of any drug
product identified in this docket, or any IRS product, that is not the
subject of an approved NDA or ANDA is unlawful as of the effective date
of this notice (see EFFECTIVE DATE). Any person who wishes to determine
whether this notice covers a specific product should write to Amber
McKinley at the Center for Drug Evaluation and Research (see FOR
FURTHER INFORMATION CONTACT). Firms should be aware that, after the
applicable date of this notice (see EFFECTIVE DATE), FDA intends to
take enforcement action without further
[[Page 31464]]
notice against any firm that manufactures or ships in interstate
commerce any unapproved product covered by this notice.
IV. Discontinued Products
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 <a href="/cdn-cgi/l/email-protection#88edccdac4dbc8eeece9a6e0e0fba6efe7fe"><span class="__cf_email__" data-cfemail="b5d0f1e7f9e6f5d3d1d49bddddc69bd2dac3">[email protected]</span></a>. In addition to the required update, firms
can also notify the Agency of product discontinuation by sending a
letter, signed by the firm's chief executive officer and fully
identifying the discontinued product(s), including the product National
Drug Code number(s), and stating that the manufacturing and/or
distribution of the product(s) have been discontinued. The letter
should be sent electronically to Amber McKinley (see FOR FURTHER
INFORMATION CONTACT). FDA plans to rely on its existing records,
including its drug listing records, the results of any future
inspections, or other available information, when it identifies
violative products for enforcement action.
Grace R. Graham,
Deputy Commissioner for Policy, Legislation, and International Affairs.
[FR Doc. 2026-10479 Filed 5-26-26; 8:45 am]
BILLING CODE 4164-01-P
</pre><script data-cfasync="false" src="/cdn-cgi/scripts/5c5dd728/cloudflare-static/email-decode.min.js"></script></body>
</html>Indexed from Federal Register on May 27, 2026.
This is legal information, not legal advice. Laws vary by jurisdiction and change frequently. Always verify current law with official sources and consult a licensed attorney in your jurisdiction for advice on your specific situation.