Then and Now: What We Have Learned From the WHI.

Area of Science:

• Endocrinology
• Gynecology
• Preventive Medicine

Background:

• The Women's Health Initiative (WHI) studies provide critical data on menopausal hormone therapy (MHT).
• Understanding MHT's long-term risks and benefits is crucial for postmenopausal women's health.
• Evolving clinical practice requires updated insights into MHT's complex effects.

Purpose of the Study:

• To review key findings from the WHI studies on menopausal hormone therapy (MHT).
• To provide a balanced assessment of MHT risks and benefits in postmenopausal women.
• To highlight critical learning points for current clinical decision-making.

Main Methods:

• A comprehensive literature search of PubMed was performed.
• Keywords included MHT, bone health, cardiovascular disease, cancer, and cognitive outcomes.
• Included studies comprised clinical trials, observational studies, and systematic reviews.

Main Results:

• MHT (CEE-MPA and CEE-only) significantly reduces fracture risk, enhanced by calcium and vitamin D.
• Cardiovascular benefits are timing-dependent: early initiation (before 60) may be protective, while late initiation increases risks.
• CEE-MPA increases breast cancer risk; estrogen-only therapy shows a non-significant reduction. Both regimens reduce colorectal cancer.
• Early MHT initiation does not affect cognition, but late initiation increases dementia risk.

Conclusions:

• WHI findings emphasize individualized and time-sensitive MHT prescriptions.
• MHT benefits and risks are influenced by formulation, timing of initiation, and patient specifics.
• These insights are integral to current and future MHT clinical guidelines.