Are the warnings on Hormone Replacement Therapy (HRT) being taken off?

Are Warnings on HRT Being Removed?

No, the warnings on HRT are not being removed—they remain firmly in place on FDA drug labels and in current clinical guidelines, though the clinical approach to HRT has evolved significantly to emphasize appropriate patient selection, timing, and duration rather than blanket avoidance. 1, 2, 3

Current Status of HRT Warnings

FDA-Mandated Warnings Remain Unchanged

The FDA drug labels for progesterone-containing HRT products continue to carry boxed warnings for:

• Cardiovascular risks: Increased risk of stroke (33 vs 25 per 10,000 women-years), myocardial infarction, and coronary heart disease events 3
• Venous thromboembolism: 2-fold increased rate of VTE (35 vs 17 per 10,000 women-years), with statistically significant increases in both DVT (26 vs 13 per 10,000 women-years) and PE (18 vs 8 per 10,000 women-years) 3
• Breast cancer: Increased risk with estrogen-progestin therapy (relative risk 1.24, with 41 vs 33 cases per 10,000 women-years) 3
• Probable dementia: Relative risk of 2.05 for women aged 65-79 years on estrogen-progestin therapy 3
• Endometrial cancer: Increased risk with unopposed estrogen (2 to 12 times greater than non-users) 3

What Has Changed: Clinical Context, Not Warnings

The evolution in HRT guidance reflects refined understanding of risk stratification rather than removal of warnings:

The "timing hypothesis" has emerged as critical: HRT initiated within 10 years of menopause or before age 60 has a more favorable benefit-risk profile compared to initiation in older women or those further from menopause 1, 2, 4

Current guideline recommendations from the American College of Obstetricians and Gynecologists, North American Menopause Society, and American Heart Association explicitly state:

• Against use for chronic disease prevention: HRT should not be used for primary or secondary prevention of cardiovascular disease or osteoporosis as the sole indication 5, 1
• For symptom management only: HRT is appropriate for moderate to severe vasomotor symptoms (hot flashes, night sweats) and genitourinary symptoms in appropriately selected women 1, 2
• Lowest dose, shortest duration: Use the minimum effective dose for the shortest time necessary 5, 1, 2

Risk-Benefit Framework That Guides Current Practice

Absolute Risk Numbers (Per 10,000 Women-Years)

For women aged 50-79 taking estrogen-progestin for 1 year 5, 1:

Harms:

• 7 additional CHD events
• 8 more strokes
• 8 more pulmonary emboli
• 8 more invasive breast cancers

Benefits:

• 6 fewer colorectal cancers
• 5 fewer hip fractures

The Critical Age/Timing Distinction

Women under 60 or within 10 years of menopause with bothersome symptoms may benefit from HRT, as cardiovascular risks appear lower in this population and symptom relief improves quality of life 1, 2, 4

Women over 60 or more than 10 years past menopause face substantially higher risks, particularly for stroke and cardiovascular events, making HRT initiation contraindicated for chronic disease prevention 2

Absolute Contraindications That Remain

The following contraindications are non-negotiable per current guidelines 2:

• History of breast cancer
• Coronary heart disease
• Previous venous thromboembolic event or stroke
• Active liver disease
• Antiphospholipid syndrome or positive antiphospholipid antibodies
• Hormone-sensitive cancers

Preferred Formulations to Minimize Risk

Transdermal estradiol patches should be first-line choice over oral formulations, as they avoid hepatic first-pass metabolism and demonstrate more favorable cardiovascular and thrombotic risk profiles 2, 4

Micronized progesterone (200 mg daily) is the preferred progestin choice for women with an intact uterus, as it lacks the antiapoptotic properties on breast cells seen with synthetic progestins 2, 4

Common Clinical Pitfalls

Initiating HRT after age 65: This is explicitly contraindicated for chronic disease prevention and increases morbidity and mortality. Women already on HRT at age 65 should be reassessed for necessity and consideration given to discontinuation 2

Using HRT solely for osteoporosis or cardiovascular prevention: This remains inappropriate, as alternative therapies (bisphosphonates, statins, lifestyle modifications) provide benefits without HRT's risks 5, 1

Failing to reassess duration: Women should not continue HRT indefinitely without regular reassessment of the ongoing need versus accumulated risks, particularly breast cancer risk which increases with duration 5, 1

Using unopposed estrogen in women with intact uterus: This dramatically increases endometrial cancer risk and is contraindicated 1, 3

The Bottom Line on Warnings

The warnings have not been removed or softened—the U.S. Preventive Services Task Force maintains its Grade D recommendation (recommend against) for routine use of estrogen-progestin for chronic disease prevention in postmenopausal women 5. What has evolved is the recognition that appropriately selected younger women with bothersome menopausal symptoms may derive meaningful quality-of-life benefits that outweigh risks when HRT is used at the lowest effective dose for the shortest necessary duration, preferably with transdermal estradiol and micronized progesterone 1, 2, 4.