Novel Menopause Perspectives & Data

As the name suggests, the Novel Menopause Perspectives & Data session provided some truly thought-provoking insights from three global experts.

Changes in intervertebral discs with menopause and HRT  - Mark Brincat

Mark Brincat opened with data relating to HRT and its effects on the intervertebral discs in post-menopausal women.

Intervertebral discs, Mark argued, are components of the spine that have been largely overlooked, despite fractures being very common. Acting as shock absorbers in the spine, the loss of the discs increases fracture risk and occurs rapidly following the menopause.  

The loss of intervertebral discs during and after menopause is due to the changes in the composition of the complex connective tissue consisting of glycosaminoglycans. Previous studies had demonstrated that disc height can be increased with HRT - with data showing a dose-dependent relationship.  

In this cross-sectional study, patients were recruited from a large bone densitometer directory. They were divided into categories according to whether they were pre-menopausal women, untreated post-menopausal women or women on calcium supplements, HRT or strontium ranelate.

Results showed a statistically significant difference in intervertebral disc height compared with patients not receiving treatment. Thus, HRT seems to have a protective effect on the intervertebral disc height loss which occurs after menopause.

However, additional studies are needed to determine whether intervertebral disc height can be used as an additional parameter to predict the risk of vertebral fracture in post-menopausal women.

Prevention, gynaecologists at the front-line - Lydia Marie-Scemama

Cardiovascular disease has become the first cause of mortality among women, and the non-medical population is in general unaware of this. This aspect of women’s health has been neglected up to now, because it was strongly believed that women were protected by female hormones. We also know that clinical signs in women are different from those of men.

In order to raise awareness and proceed, Lydia suggested:

  • Scientific societies involved in cardiology and gynaecology/obstetrics work together to inform women of the dangers of CVD.
  • Inform colleagues through the medical media and meetings.
  • Target GPs especially, creating a multidisciplinary net around each patient.

Lydia and her colleagues created an action plan in the form a flyer - this was designed to increase the impact on doctors and patients. Elected representatives from across disciplines and industries were enlisted to enforce and change attitudes. This, Lydia argued, is a big step in preventing CVD in women.

Alzheimer disease, why should oestrogens work? - Paulin Villaseca

Oestrogens have consistently demonstrated neuroprotective effects in cellular and animal studies. In monkey studies, when estradiol is low in the cycle, dendrite spines are few. When estradiol is increased, the relationship is reversed and dendrite spines grow.

To determine any intervention in dementia in humans, it will require decades of follow-up, plus the complexity of confounding factors must also be considered. Paulin argued that the study of estradiol could assess the efficacy of preventative strategies.

The initiating pathological factor of Alzheimer's disease (AD) is the amyloid-beta peptide (AB), formed from the precursor protein (APP). APP is proteolysed by enzymes known as secretases: alpha-secretase cuts the AB peptide in the middle of its sequence, destroying its capacity to aggregate and trigger AD. Conversely, beta-secretase releases the peptide, facilitating aggregation.

Estradiol simulates alpha-secretase and inhibits beta-secretase - reducing the capacity for APP to aggregate into amyloid plaques.

Additionally, estradiol inhibits a second pathway, involving Tau proteins. Microtubules require Tau proteins to stabilise their structure and function. In AD, kinases phosphorylate the Tau, destabilising the microtubules and leading to neuronal death. The phosphorylation step is inhibited by estradiol.

Estradiol is a key player in each of these mechanisms and Paulin expressed a keen interest for this to be explored therapeutically.