Hormone replacement therapy has helped millions of women around the world to ease their menopausal symptoms, but controversy lingers about whether it also increases their chances of developing cancer and stroke. Could a newly discovered Chinese yam protein provide a safer alternative?

Non-menopausal women have a finite number of follicles or 'immature egg cells' inside their ovaries. Within each follicle, granulosa cells surround the immature egg and are involved in the egg's maturation and in the production of oestrogen and progesterone, the 2 major types of female sex hormones. Natural menopause occurs when the follicles have all been used up or have degenerated, which also causes the levels of oestrogen and progesterone to drop.

In addition to the typical menopausal symptoms that most women experience to some extent for many years, their drop in oestrogen could also come with higher risks of developing health problems such as heart disease, osteoporosis or 'thinning bones', cognitive decline, and others.

Doctors often prescribe hormone replacement therapy (HRT) to help menopausal patients whose quality of life has decreased noticeably because of their symptoms. HRT helps to restore oestrogen levels. However, depending on the type of HRT used to meet individual patients' circumstances, there could be side effects, such as raising users' risks of developing breast cancer, uterine cancer, ovarian cancer, venous thromboembolism (a blocked vein owing to a part of a blood clot breaking off), or stroke. Different kinds of HRT also come with different efficacies and risks for different health problems.

But a safer alternative could be on the horizon. In a study co-authored by Dr Patrick Lai Yau-ming, Assistant Professor at PolyU's Department of Health Technology and Informatics, a previously unknown protein in a type of Chinese yam has been found to increase the formation of oestradiol, the most potent kind of oestrogen, in rat granulosa cells without increasing the number of breast cancer and ovarian cancer cells.

In China, the Dioscorea opposita species (Dioscorea opposita Thunb.; "shan yao"; 薯蕷; 淮山; 土薯; 山薯) of Chinese yam is the most commonly used of the genus 'group' of Dioscorea species for improving female health and regulating menstruation. Furthermore, the rhizome part of the stem of the species has been classified as a Chinese herbal medicine by the Chinese government.

Previous studies showed that Dioscorea extract seemed to ease menopausal symptoms, with higher levels of oestrogen detected. So Dr Lai and his co-authors from institutions in Hong Kong, mainland China and the Netherlands decided to study protein extract from rhizomes of the Dioscorea opposita species.

Oestradiol and Progesterone Increase

They isolated the protein and analysed its chemical and biological characteristics. Chemically, they found the protein was novel and designated the moniker "DOI" to it. Biologically, they found DOI stimulated the formation of oestradiol in rat granulosa cells in vitro and there was an increase in the number of granulosa cells.

No Rise in Breast Cancer and Ovarian Cancer Cells

The body weights of the rats did not change significantly during the in vivo experiment, implying that DOI was not toxic to the rats. Notably, DOI did not stimulate a rise in the number of breast cancer and ovarian cancer cells, which suggests that DOI could be a more effective and safer alternative to HRT.

Could Counteract Other Ageing Problems

In addition, the study suggested that some health problems which many menopausal women face could be lessened by DOI. Menopause and ageing in general are usually accompanied by a decline in the women's immune function. The team discovered that DOI enhanced the proliferation of mouse splenocytes in vitro, which are white blood cells that originate in mice spleens and help the animals to fight off infections. Furthermore, they found that DOI could counteract the progression of osteoporosis and increase bone mineral density.

The team also suggested that DOI could help to hinder cognitive decline associated with menopause because more brain-derived neurotrophic factor (BDNF) and its TrkB receptor were detected in the rats' prefrontal cortex, perhaps by way of DOI's stimulating the production of oestradiol since the hormone is neuroprotective and can increase the quantity of BDNF. BDNF is involved in the growth, maturation and maintenance of neurons, and assists in enabling synapses (the junctions between neurons) to adapt their strengths of connection between neurons, which is important in learning and memory.