Transdermal Hormone Therapy Best Protects Bone Health in Women With FHA: Study - Video

Hormone replacement therapy (HRT) delivered through the skin is the most effective way to protect bone health in women whose periods have stopped due to anorexia or intense exercise, according to new research from Imperial College London and Imperial College Healthcare NHS Trust.

The findings come from a large meta-analysis that reviewed all available randomised clinical trials on treatments for Functional Hypothalamic Amenorrhea (FHA). FHA is a common reproductive condition in which menstrual periods stop due to low energy availability caused by eating disorders such as anorexia nervosa or excessive physical activity. It accounts for nearly one-third of all cases of amenorrhea.

When periods stop, estrogen levels fall sharply, leading to rapid bone loss. Around 50% of women with FHA have low bone mineral density, compared with just 1% of healthy women, and their risk of fractures can be up to seven times higher.

Doctors initially aim to restore periods through lifestyle changes such as improved nutrition, reduced exercise, and psychological support. However, these approaches often fail. While international guidelines recommend estrogen therapy, there has been limited evidence on which type works best.

To address this gap, researchers analysed data from 692 women across multiple trials, making it the largest review of its kind. They compared oral HRT, transdermal HRT (applied via patches or gels), the combined oral contraceptive pill, and teriparatide, a bone-building drug.

The study found that transdermal HRT and teriparatide significantly improved bone mineral density, with gains of 2% to 13% over one to two years. In contrast, oral HRT and the oral contraceptive pill showed no meaningful benefit for bone health.

The findings have immediate clinical relevance. A recent UK audit found that many women with FHA are still prescribed the oral contraceptive pill, which this study suggests is ineffective for preventing bone loss.

Experts said the results could improve care across multiple specialties, including general practice, endocrinology, gynaecology, and psychiatry. Researchers stressed that women should discuss treatment options with their GP or bone specialist to ensure early and effective protection of long-term bone health.

REFERENCE: Efthymiadis, A., et al. (2026) Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials. The Journal of Clinical Endocrinology & Metabolism. DOI: 10.1210/clinem/dgag005. https://academic.oup.com/jcem/advance-article/doi/10.1210/clinem/dgag005/8417524