Given that MS is three times more common in women than men, and that the average age of MS onset is between the ages of 20 and 40, the majority of females with MS are going to go through “the change” after their MS diagnosis. It is therefore vital that we are aware of the potential effects of one on the other, and if anything can be done to improve the situation. After all, living with MS can be difficult enough, without adding menopause into the mix.
What is the menopause?
Menopause is technically defined as the absence of periods for 12 consecutive months or more. It is caused by a marked reduction in blood levels of the sex hormone; oestrogen, and marks the end of the reproductive phase of a woman’s life. But it is much more than a time-limited point on a calendar, because the symptoms of perimenopause (the time around the cessation of periods) can last for on average three to five years, and as listed above, can be very difficult to manage. The risk of developing other health conditions such as heart disease, stroke and osteoporosis, also significantly increases after the menopause.
Oestrogen and HRT
Oestrogen is the primary culprit of common menopausal symptoms, and it is here that the cross-over with MS begins. It is well known that high levels of oestrogen (e.g. pregnancy and breast-feeding) are associated with a potent anti-inflammatory effect on the immune system. In pregnancy, especially the second trimester, there can be a marked improvement in many auto-immune conditions, including rheumatoid arthritis, lupus, psoriasis, and you guessed it, MS. Unfortunately, there is often a flare-up of symptoms again post-pregnancy, as oestrogen levels fall. So high levels of oestrogen are anti-inflammatory, and low levels appear to be pro-inflammatory. There is also evidence to show that high levels of oestrogen have a directly protective and anti-degenerative effect on cells in the brain.
This fits in with what was previously known about MS after the menopause, where previous research has described worsening symptoms and increasing disability levels; but these studies have tended to be small, and the data, self-reported. The medical guidance has always been cautious, and generally only to take HRT to treat menopausal symptoms, rather than to provide a potential benefit in other conditions, including MS.
It has led to the inevitable conclusion for many women with MS, “should I just take HRT then?!” It seems logical at a basic science level, it is very effective at reducing the unpleasant menopausal symptoms and may even be protective against future progression of MS. Unfortunately, it is not quite as simple as that, because whilst the benefits of HRT, in terms of menopausal symptoms, risk of heart disease and osteoporosis are well known, there are also potential risks involved. It is a complicated and often contradictory subject, but the latest evidence, published in the Lancet, specifically shows that HRT use does increase one’s risk of breast cancer.
In the U.K. for example, around 1 in 16 women who have never taken HRT will be diagnosed with breast cancer between the ages of 50 and 69. For women with a normal body mass index (BMI) who start HRT in their 40s or 50s, the latest analysis found their additional risk of breast cancer was 1 in 200 for oestrogen-only HRT, and between 1 in 50 and 1 in 70 for those taking various preparations containing both oestrogen and progesterone.
Whilst this may cause alarm, women should be counselled that other factors, including BMI and alcohol consumption, have a far greater impact on breast cancer risk than HRT. For example, the extra risk of breast cancer associated with being overweight or obese is six times higher than the extra risk associated with combined HRT. It is also extremely important to note that this research only studied the number of breast cancer cases, not any effects of HRT on mortality rates. Nor did it compare the relative risk of breast cancer for women taking HRT with that of women of the same age with normal ovarian function, therefore giving a misleading presentation of the risk.
Nevertheless, these risks may make HRT use unacceptable to some, even if it may perhaps have a positive impact on their MS. For others, these risks make it even more important to understand any direct effects of the menopause on MS, to allow for an informed decision to be made.
MS and the Menopause
Fortunately, a recent study from a team of researchers in Lisbon, Portugal, has shed some more light on the issue.
In this retrospective, longitudinal cohort study, 37 postmenopausal females, all over 44 years of age, with an MS diagnosis at least 12 months prior to menopause, were recruited.
They were evaluated every three to six months and followed up for at least 12 months. Data was collected on premenopausal and postmenopausal disability levels (EDSS — Expanded Disability Status Scale), rates of disease progression pre and postmenopause, and annualised relapse rate (ARR). They also noted if each patient had undergone a natural or surgical menopause, and whether disease modifying therapies (DMT) and any form of HRT was used.
The results showed that following menopause, the ARR was reduced, while EDSS progression rates and frequency of progression events were unchanged from the premenopausal period.
These findings persisted in those patients who had changed or had not changed their DMT during the study period, in those who had other health conditions, and regardless of MS disease duration. This is reassuring, as all of these factors could have had independent effects on MS activity, and therefore influenced the results.
There were however, some notable limitations of the study. The small sample size prevented analysis of other potential factors involved in disease activity and progression after menopause, namely the use of HRT. Its retrospective design and follow-up based on registries could also potentially have allowed for recording bias to have occurred. Future studies should also include women younger than 45 years or a control group of men, in order to separate the effects of menopause on MS, from those of aging itself.
In conclusion, this study suggests that after menopause, there is a reduction in relapse rates, but also that disability progression persists at a similar rate to the premenopausal period.
This should offer some reassurance, as it has previously been suggested that disability progression rates tend to increase postmenopause. And whilst this alone may be enough evidence for some OMSers to hold off on HRT use for purely MS-related reasons, it emphasises the urgent need for larger, prospective studies into the currently unknown effects of HRT on long-term MS outcomes. Only then can a truly informed choice be made.
We will of course keep you up to date with any future developments.
- DOI: 10.1159/000496374
- Collaborative Group on Hormonal Factors in Breast Cancer - Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet2019;394:1159-68. doi:10.1016/S0140-6736(19)31709-X pmid:31474332