Topical HRT protects bone density in women whose periods stop due to anorexia or intense exercise
Researchers at Imperial College London and Imperial College Healthcare NHS Trust have discovered that hormone replacement therapy (HRT) applied to the skin is the best way to protect bone density in women with a condition called functional hypothalamic amenorrhoea (FHA) - where periods have stopped due to anorexia or intense exercise.
This new meta-analysis - where several previous clinical trials in this area are analysed together - identified applying HRT to the skin is the most effective way to treat women with FHA. The study has been published in the Journal of Clinical Endocrinology and Metabolism.
FHA is a common reproductive condition, explaining almost a third of cases of menstrual periods stopping. The resulting lack of the natural hormone oestrogen can affect the body physically, particularly bone mineral density. Around half of affected women with FHA suffer from low bone mineral density, compared to only 1% of healthy women, and their risk of bone fractures is up to seven times higher than in the general population.
Identifying the most effective treatment – and it’s not the oral contraceptive pill
When women are diagnosed with FHA, doctors will first try to restore menstrual periods through lifestyle changes, including psychological and dietary interventions, but these are often unsuccessful. International clinical guidelines then recommend giving hormone replacement therapy (HRT) containing oestrogen, but until now, it was unclear which form is best.
In this study, the team reviewed all previous randomised clinical trials involving 692 people overall - the largest dataset of its kind - and examined the various therapies available, focusing on their impact on bone mineral density at different sites in the body. As well as looking at different formulations of HRT (oral and transdermal) they investigated teriparatide, a prescription bone-building agent that can be used to treat severe osteoporosis.
They found that:
- HRT delivered through the skin and teriparatide increased bone mineral density, between 2 and 13%
- No significant benefit was observed for oral HRT or the combined oral contraceptive pill.
The study has immediate implications for frontline clinical care. A recent UK audit found that around a quarter of women with anorexia-related FHA are prescribed the oral contraceptive pill to address bone loss. This study suggests such treatment should be replaced by more effective alternatives like transdermal HRT.
Helping women to get the right treatment, sooner
Senior author of the study and consultant endocrinologist at the Trust Professor Alexander Comninos said: “Bone density is lost very rapidly in FHA and so addressing bone health early is very important to reduce the lifelong risk of fractures. Our study provides much needed comparisons of all the available treatments from all available studies.
“Clearly the best treatment is to restore normal menstrual cycles and therefore oestrogen levels through various psychological, nutritional or exercise interventions - but that is not always possible. The foundation for bone health is good calcium and vitamin D intake (through diet and/or supplements) but we have additional treatments that are more effective.”
“Our goal is simple: to help women receive the right treatment sooner and to protect their bone health in the long-term. We hope this study provides clinicians with better evidence to choose transdermal oestrogen when prescribing oestrogen and so inform future practice guidelines. Right now, millions of women with FHA may not be receiving the best treatments for their bone health.”
The results could drive immediate improvements in how a wide range of specialists - from endocrinologists, GPs, rheumatologists, gynaecologists to psychiatrists - treat the disorder.
Patients considering their treatment plan should speak to their GP or bone health specialist in the first instance and before making any decisions.
The researchers were supported by grants from the Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR), with wider support from the NIHR Imperial Biomedical Research Centre (BRC).
