Vikram Sinai Talaulikar: Long-Term Associations of Postmenopausal HRT Are Not “One-Size-Fits-All”

Vikram Sinai Talaulikar, Specialist in Reproductive Endocrinology at The LUNA Clinic, shared a post on LinkedIn about a paper by Ting-Fang Lu et al. published in Human Reproduction Open:

“Here is an observational real-world cohort study from Ting-Fang Lu et al. looking at long-term systemic outcomes of postmenopausal hormone replacement therapy by age at menopause.

Researchers used data from the TriNetX Research Network, which provided access to electronic medical records for ∼111 million patients globally.

Women who initiated postmenopausal HRT containing oestrogen and/or progestogen within 1 year after menopause diagnosis were propensity score-matched 1:1 with non-users using baseline demographic, clinical, and laboratory covariates.

Primary matching yielded 83 670 matched pairs in women who experienced menopause at age ≤60 years and 12 175 matched pairs in women who experienced menopause at age >60 years. To ensure adequate time for the development of hard clinical endpoints, researchers required that the index event (initial menopause diagnosis) occurred at least 10 years before data extraction (31 December 2025), thereby guaranteeing a minimum follow-up period of one decade.

In the overall matched cohort of women experiencing menopause at age ≤60 years – compared with non-users, postmenopausal HRT was associated with lower hazards of type 2 diabetes and cardiovascular disease CVD. Skeletal health was preserved, evidenced by a lower hazard of compression fractures.

HRT was associated with lower hazards of breast cancer, colorectal cancer and venous thrombosis VTE. In the primary age-stratified model, the >60-year cohort showed a higher breast cancer hazard.

These findings have major limitations – residual confounding, incomplete socioeconomic and screening data, limited details on HRT formulation, route, dose and duration, unavailable breast cancer subtype information and unavailable exact maximum follow-up duration.

But the take home message is that the long-term associations of postmenopausal HRT are not ‘one-size-fits-all’ but depend strongly on age at menopause.

In this analysis with all its limitations, postmenopausal HRT was associated with lower chances of heart disease, bone fractures, and blood clots. However, its association with breast cancer varied substantially by age. For women who experienced menopause prematurely (under age 40), postmenopausal HRT was associated with a lower breast cancer hazard.

By contrast, among women who reached menopause after age 60, initiating postmenopausal HRT was associated with a higher breast cancer hazard.

Observational studies don’t necessarily prove or disprove theories or conclusions. But every little evidence adds to our understanding of long-term effects of HRT and are valuable in counselling patients on benefits and risks.”

Title: Long-term systemic outcomes of postmenopausal hormone replacement therapy by age at menopause: a real-world cohort study

Authors: Ting-Fang Lu, Chien-Hsing Lu, Yu-Hsiang Shih, Yen-Fu Chen, Chun-Ting Fan, Shao-Jing Wang, Shih-Tien Hsu, Chih-Ku Liu, Lou Sun, Sheau-Feng Hwang, Tsung-Hsien Lee

You can read the Full Article in Human Reproduction Open.

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