Hormone replacement therapy (HRT) applied via the skin is emerging as the most effective method for safeguarding bone density in women whose menstrual cycles have ceased due to anorexia or intense physical activity. This revelation comes from a comprehensive study conducted by researchers at Imperial College London and Imperial College Healthcare NHS Trust.
The study, a meta-analysis of previous clinical trials, focuses on women with Functional Hypothalamic Amenorrhoea (FHA), a prevalent reproductive disorder where menstruation stops due to anorexia nervosa or excessive exercise. FHA accounts for nearly a third of cases where menstrual periods halt, leading to a significant reduction in natural oestrogen levels, which in turn affects bone mineral density.
Understanding the Impact of FHA on Bone Health
Approximately 50% of women with FHA experience low bone mineral density, a stark contrast to the 1% prevalence among healthy women. This condition also increases the risk of bone fractures by up to seven times compared to the general population.
Initial treatment for FHA typically involves lifestyle modifications aimed at restoring menstrual cycles, such as psychological and dietary interventions. However, these approaches often fall short. Consequently, international clinical guidelines advocate for HRT containing oestrogen, though the optimal form of administration has been unclear until now.
Evaluating Treatment Options
The research team reviewed all existing randomized clinical trials involving 692 individuals, the largest dataset of its kind, to assess the impact of various therapies on bone mineral density across different body sites. The study compared oral and transdermal HRT formulations, as well as teriparatide, a prescription bone-building agent for severe osteoporosis.
- Transdermal HRT and teriparatide showed clinically significant improvements in bone mineral density, with increases ranging from 2-13% over 1-2 years, depending on patient characteristics, treatment choice, and body site.
- No significant benefit was noted for oral HRT or the combined oral contraceptive pill.
This finding has immediate implications for clinical practice, especially since a recent UK audit revealed that about 25% of women with anorexia-related FHA are prescribed the oral contraceptive pill to address bone loss. The study suggests that such treatment is suboptimal and should be replaced by more effective alternatives like transdermal HRT.
Expert Insights and Future Directions
The study’s authors emphasize the need for improved clinical guidelines based on these findings. “This study provides much-needed evidence to improve practice and underpin future bone guidelines for this common condition,” the researchers stated, highlighting the potential for immediate improvements in treatment approaches across various medical specialties.
Dr. Agathoklis Efthymiadis, a Clinical Research Fellow at Imperial College London, remarked, “Our study provides robust data to improve the management of this condition and inform practice guidelines. Given the present fragmented management of women with amenorrhoea, we believe this will be of interest not just to GPs but to a wide range of specialists, from gynaecologists, rheumatologists, and endocrinologists. Our goal is simple: to help women receive the right treatment sooner and to protect their bone health in the long-term.”
The researchers also engaged with women affected by FHA from the Imperial Endocrine Bone Unit at St Mary’s Hospital, incorporating their insights into the study. Professor Alexander Comninos, the senior author and a Consultant Endocrinologist at Imperial College Healthcare NHS Trust, underscored the urgency of addressing bone health early to mitigate lifelong fracture risks.
Scientific Rationale and Future Research
The study highlights the advantages of transdermal oestrogen over oral forms. “Oral oestrogens can reduce certain bone-forming hormones, whereas transdermal oestrogens do not,” the researchers explained. This distinction is crucial as oral oestrogens typically result in lower ‘active’ oestrogen levels compared to their transdermal counterparts.
Professor Comninos added, “We hope this study provides clinicians with better evidence to choose transdermal oestrogen when prescribing oestrogen and so inform future practice guidelines. This is important as millions of women with FHA may not at present be receiving the best treatments for their bone health.”
The study’s findings underscore the need for further research, particularly large-scale studies comparing different forms of oestrogen and progesterone in women with varying causes of FHA, such as those linked to intense exercise or anorexia nervosa.
The research received support from the Medical Research Council (MRC) and the National Institute for Health and Care Research (NIHR), with additional backing from the NIHR Imperial Biomedical Research Centre (BRC).
