MS in Men and Women: The Role of Sex Hormones in Women

Patient Expert

First, we discussed some differences between men and women who develop multiple sclerosis.   Next we explored how hormones, specifically testosterone, play a significant role in men who develop MS.   Today we're going to explore the hormones testosterone and estradriol as they affect brain damage in women with MS.

Estrogen hormones affect female sexual development and function.   Both men and women produce estrogen at varying amounts.   The most important types of estrogen hormones include estradiol, estriol, and estrone.   Estrogen hormones are produced in the ovaries and in the placenta during pregnancy.   Just like testosterone, small amounts are produced by the adrenal glands in both genders.

Estradiol is the most commonly measured type of estrogen for non-pregnant women.   Levels vary during the menstrual cycle and drop to a very low level after menopause.   Estriol is produced in large amounts by the placenta during pregnancy and can be detected in the blood and urine.   Estrone can be used to measure estrogen levels in women who have gone through menopause.

Just as in men, sex hormones can provide neuroprotective effects in women who have MS.

Brain Lesions and Sex Hormones
During a study looking at sex hormones and MRI features, researchers found that the mean number of gadolinium-enhancing lesions was significantly higher in women than in men, while the extent of brain damage was similar on T1 and T2 weighted MRI scans.   T1 hypointense lesions ("black holes") indicate axonal loss and are strongly correlated with neurological disability in MS.   T2 hyperintense lesions can indicate various pathologies, ranging from edema and inflammation to demyelination and axonal loss.

According to the study, sex hormones, including estradiol, testosterone, and DHEA, were measured during the follicular (3rd to 9th days) and luteal phases (21st to 28th days) of the women's menstrual cycle.   Progesterone was only measured during the luteal phase.   During the study, no significant difference was observed in the frequency of enhancing lesions between scans obtained in women during the follicular and luteal phases.   Women with MS had lower testosterone concentrations than healthy controls in both the follicular and luteal phases of the menstrual cycle.

Testosterone, Not Just for Men
Using a normal score for testosterone levels of healthy women, researchers identified women with MS who had abnormally low testosterone concentrations.   A greater number of gadolinium-enhancing lesions were found in the seven women (of 35 total in the study) with abnormally low testosterone levels as compared to those with normal levels.

However, higher serum levels in women with MS were associated with more "black hole" lesions but not T2 hyperintense lesions.   A relationship between higher testosterone concentrations and neurological disability was found, and no significant correlation was found between MRI data and estradiol concentrations.

If I am reading this correctly (and yes, I had to go over the study several times to truly understand), testosterone levels which are too low in women with MS may increase the number of gadolinium-enhancing lesions.   Testosterone levels which are too high may increase "black holes" and neurological disability.   Estradiol level didn't seem to effect lesion load in women with MS.

I guess, just like Goldie in Goldilocks and the Three Bears, it seems women with MS need to have testosterone levels which are "just right."

In the next post, we will explore the role that the pregnancy hormone estriol has in women with MS.

RESOURCES: Whitacre CC, Reingold SC, O'Looney PA, et at., Task Force on Gender, Multiple Sclerosis and Autoimmunity.   A Gender Gap in Autoimmunity, Supplementary Material.   Science, 1999 Feb 26;283(5406):1277-8.

Voskuhl RR. Gender issues and multiple sclerosis.   Curr Neurol Neurosci Rep, 2002 May;2(3):277-86.

Tomassini V, Onesti E, Mainero C, et al. Sex hormones modulate brain damage in multiple sclerosis: MRI evidence.   J Neurol Neurosurg Psychiatry, 2005;76:272-275.

Gold SM and Voskuhl RR. Estrogen and Testosterone Therapies in Multiple Sclerosis.   Prog Brain Res, 2009 ; 175: 239-251.

More hormone/testosterone info can be found the Multiple Sclerosis Resource Centre website.