FDA updates labels on multiple menopausal hormone therapies

The FDA on February 12, 2026, approved 6 drug label changes to menopausal hormone therapy products, or hormone replacement therapy (HRT), to clarify risk considerations for the drugs, the federal agency announced in a press release.¹

More specifically, risk statements related to cardiovascular disease, breast cancer, and probable dementia were removed from the FDA’s most prominent safety-related “boxed warning.”

The HRTs with updated prescribing information included²:

• Progesterone, USP capsules 100 mg & 200 mg (PROMETRIUM) (Progestogen alone)
• Estradiol gel, for topical use (DIVIGEL) (Systemic estrogen alone)
• Synthetic conjugated estrogen, A tablets for oral use (CENESTIN) (Systemic estrogen alone)
• Synthetic conjugated estrogens, B tablets for oral use (ENJUVIA) (Systemic estrogen alone)
• Estradiol vaginal system (ESTRING) (Topical vaginal estrogen)
• Estradiol and progesterone capsules for oral use (BIJUVA) (Systemic estrogen and progestogen)

According to the FDA announcement, the federal agency initiated the removal of these warnings in November 2025 after a “comprehensive review of the scientific literature. At the FDA’s request, 29 drug companies have submitted proposed labeling changes,” the agency stated.¹

The first 6 products with approved labeling changes range across the 4 categories of HRT for menopausal women, specified above next to each product.

The FDA wrote that multiple hormone therapies for moderate-to-severe hot flashes, vaginal dryness and discomfort, and preventing bone loss are approved, though in 2020, of approximately 41 million women in the United States aged 45-64 years, approximately 2 million received a hormone-therapy prescription.

“Today’s action will allow women, working with their health care professionals, to make better-informed decisions about their treatment plan for menopause symptoms,” wrote the FDA in the announcement.

For full label updates and details related to each drug listed above, click here.

Below, find updated contraindications for the updated labels announced by the FDA.

Contraindications for 6 menopausal HRTs

DIVIGEL³:

• Abnormal genital bleeding of unknown etiology
• Current or history of breast cancer
• Estrogen-dependent neoplasia
• Active DVT, PE, or history of these conditions
• Active arterial thromboembolic disease
• Known anaphylactic reaction, angioedema, or hypersensitivity to Divigel
• Hepatic impairment or disease
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Click here for DIVIGEL’s full prescribing information.

CENESTIN⁴:

• Abnormal genital bleeding of unknown etiology
• Current or history of breast cancer
• Estrogen-dependent neoplasia
• Active DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease
• Known anaphylactic reaction or angioedema or hypersensitivity to CENESTIN
• Hepatic impairment or disease
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Click here for CENESTIN’s full prescribing information.

ENJUVIA⁵:

• Abnormal genital bleeding of unknown etiology
• Current or history of breast cancer
• Estrogen-dependent neoplasia
• Active DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
• Known anaphylactic reaction, angioedema or hypersensitivity to ENJUVIA
• Hepatic impairment or disease
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Click here for ENJUVIA’s full prescribing information.

PROMETRIUM⁶:

• Hypersensitivity to its ingredients
• Because capsules contain peanut oil, PROMETRIUM is contraindicated in patients allergic to peanuts
• Abnormal genital bleeding of unknown etiology
• Known, suspected, or history of breast cancer
• Active deep vein thrombosis, pulmonary embolism or history of these conditions
• Active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions
• Known liver dysfunction or disease

Click here for PROMETRIUM’s full prescribing information.

ESTRING⁷:

• Abnormal genital bleeding with unknown etiology
• Known or suspected estrogen-dependent neoplasia
• Active DVT, PE, or a history of these conditions
• Active arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
• Known anaphylactic reaction or angioedema or hypersensitivity to ESTRING
• Known liver impairment or disease
• Protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders

Click here for ESTRING’s full prescribing information.

BIJUVA⁸:

Abnormal genital bleeding of unknown etiology

Breast cancer or a history of breast cancer

Estrogen-dependent neoplasia

Active deep vein thrombosis (DVT), pulmonary embolisum (PE), or history of these conditions

Active arterial thromboembolic disease (for example, stroke, myocardial infarction (MI)), or a history of these conditions

Known anaphylactic reaction, angioedema, or hypersensitivity to BIJUVA

Hepatic impairment or disease

Known thrombophilic disorders, such as protein C, protein S, or antithrombin deficiency

Click here for BIJUVA’s full prescribing information.

References:

1. FDA approves labeling changes to menopausal hormone therapy products. FDA. Press release. February 12, 2026. Updated February 12, 2026. Accessed February 12, 2026. https://www.fda.gov/news-events/press-announcements/fda-approves-labeling-changes-menopausal-hormone-therapy-products?utm_medium=email&utm_source=govdelivery
2. Menopausal hormone therapies with updated prescribing information. FDA. Updated February 12, 2026. Accessed February 12, 2026. https://www.fda.gov/drugs/drug-safety-and-availability/menopausal-hormone-therapies-updated-prescribing-information
3. DIVIGEL (estradiol gel), for topical use Initial U.S. Approval: 1975. FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/022038s017lbl.pdf
4. CENESTIN (synthetic conjugated estrogens, A) Tablets, for oral use Initial U.S. Approval: 1999. FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/020992s043lbl.pdf
5. ENJUVIA (synthetic conjugated estrogens, B) Tablets, for oral use Initial U.S. Approval: 2004. FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/021443s014lbl.pdf
6. PROMETRIUM (progesterone, USP). FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/019781s026lbl.pdf
7. ESTRING (estradiol vaginal system). FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/020472s022lbl.pdf
8. BIJUVA® (estradiol and progesterone) capsules, for oral use Initial U.S. Approval: 2018. FDA. Accessed February 12, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/210132s013lbl.pdf