Menopause, beyond obesity and metabolic disorders

Obesity is a health problem of a truly global proportion. In this session, a number of speakers offered oral presentations linking menopause to not only obesity, but also metabolic disorders and wider physiological diseases.

Here are two of the highlighted talks:

Epigenetics of Oestrogen Metabolism and Breast Cancer Risk - Jennifer Pearlman

Although tools for screening breast cancer have improved, there has been little advance in further understanding and developing preventative strategies.

The transformative process that occurs in each and every patient from normal cell to invasive ductal carcinoma is very unique. It is driven by a number of factors: genetic, metabolic, epigenetic and environmental forces all play a key role.

One of these factors that has long been a focus of attention is oestrogen. Oestrogen metabolism is a complicated and poorly understood process subject to genetic and epigenetic effects that can have vast implications on health, risk of disease and cancer. 

The metabolism of oestrogen involves a complex biphasic detoxification process that mainly occurs in the liver. The first phase involves hydroxylation; this is followed by a number of conjugation reactions. Such reactions have the potential to generate toxic intermediates including oestrogen-quinones that bind and depurinate DNA increasing mutagenicity and inducing breast cancer.

Epigenetic factors, a result of the complex relationship between our genome and environment also play a key part. Environmental exposure to certain endocrine disrupting chemicals (e.g. BPA and DES) influences the detoxifying pathways and subsequent intermediates.

Jennifer highlighted that  the ability to clinically measure potentially harmful oestrogen intermediates in women at risk holds powerful predictive value in estimating breast cancer and risk stratifying patients to high-risk, more intensive screening programs.

Effects of six-month oral DHEA supplementation on beta-endorphin response to oral glucose tolerance test in obese and non-obese early and late postmenopausal women - Andrea Giannini

Beta-endorphin is a neuropeptide involved in several brain functions, including decreasing bodily stress and maintaining homeostasis. Previously, it has been demonstrated that while in pre-menopausal women the response of plasma beta-endorphin levels to oral glucose tolerance testing is maintained, in post-menopause there is a lack of response.

Beta-endorphin, Andrea hypothesised is therefore dependent on gonadal steroids, while partly influenced by body weight.

Previous data has demonstrated that DHEA increases beta-endorphin levels in menopausal women and restores the peptide's adrenergic, serotoninergic and opiatergic neuroendocrine stimuli. DHEA is not only related increases in beta-endorphin but also beneficial changes in adrenal products, anabolic pathways and decreases in cortisol.

The aim of Andrea's study was to evaluate plasma beta-endorphin levels in response to oral glucose tolerance testing in early and late menopausal women of normal or overweight BMI, treated with oral DHEA for 6 months.

A key question was: could DHEA supplementation increase beta-endorphin and control endocrine modifications?

Results demonstrated that an increase in plasma beta-endorphin levels with DHEA supplementation was observed in both obese and non-obese women. Perhaps, Andrea suggested, DHEA should be considered more than a simple 'diet integrator' but rather an effective hormone replacement treatment.