A proactive approach to women living with Parkinson's disease- hormone replacement, pregnancy and emerging issues
Drs Subramanian, Keener and Moro along with three women currently living with Parkinson’s disease who are also health care providers— together, wrote a recent paper in Movement Disorders highlighting a number of gaps in treatment, advocacy and research for women living with Parkinson’s disease. We will summarize the findings of this paper over the next few blog posts— we realize that this “call to action” is important— and the paper contents may not be available to everyone. This blog will hopefully fill that gap. Dr. Annelien Oosterbahn focused in writing the section of this paper about “hormones,” and other critical issues. As an OBGYN living with Parkinson’s disease she has been passionate about these issues.
How common is Parkinson’s disease in men vs
women?
Parkinson’s disease is 1.4 times more common in men than in women. However, the ratio is actually lower in Asia (0.95-1.2 times more common in men than in women) possibly due to differences in the environment and/or genetic factors— or even how the study was performed. Interestingly, over the years the incidence of Parkinson’s disease in women has remained stable whereas it has increased in men. These findings collectively support an important role for sex-specific genetic and epigenetic factors in what causes Parkinson’s disease— that information may be important to help us to better understand the disease.
Are risk factors for Parkinson’s disease the same for
men and women?
Sex and gender interactions may have differential effects on several Parkinson’s disease risk factors— though there are conflicting studies. For example, caffeine consumption is linked to a lower risk of PD among men, but not women. However, among post-menopausal women, those on hormone replacement therapy who consumed caffeine actually had an increased risk of PD. In a recent study, PD risk was lower in current male smokers when compared to current female smokers— with the same level of exposure. In contrast, the PD risk-lowering effect of alcohol consumption was more pronounced in women than in men. Pesticide exposure has also been linked to the development of PD, though prior studies have found this association mostly in men and not women. Thus, more research will be required to resolve these conflicting results.
Is the hormone estrogen protective for persons with
Parkinson’s disease?
Sex differences in Parkinson’s disease epidemiology suggest that estrogen may be “neuroprotective.” In preclinical studies, estrogen has been shown to possibly protect against brain cell death and to have anti-oxidant effects. Estrogen may prevent the protein alpha-synuclein from clumping together and forming fibrils. Several studies have demonstrated that higher total lifetime estrogen exposure may be associated with a decreased risk of PD in women— although some other studies have been inconclusive.
The timing of estrogen exposure and association with sexual hormones may be critical factors: it has been shown that post-menopausal estrogen-only treatment among women with hysterectomy may increase the risk of PD when compared to “no increased risk” when women experience natural menopause and receive usual treatment— with combined estrogen-progesterone. A recent retrospective analysis showed that greater duration of hormone replacement therapy (HRT) was associated with a reduced risk of neurodegenerative disease, including PD. In contrast, however, another study of women experiencing natural menopause showed that use of hormone replacement therapy (HRT) for greater than five years was associated with an increased PD risk of 17% as compared to postmenopausal women who have never used HRT.
How does Hormone Replacement Therapy (HRT)
change the risk of later developing Parkinson’s?
The current literature reveals conflicting data on the impact of HRT on PD risk. One possible explanation lays in the complex interaction between timing and duration of hormone exposure— and the interaction with other genetic and environmental risk factors. Understanding the actual effects of reproductive factors, HRT and the Oral Contraceptive Pill (OCP) use on the risk of PD may help to identify mechanisms and pathways responsible for these effects, and to determine strategies for future prevention of PD. Currently, the effects of HRT on PD risk remain inconclusive and will require further study. The interplay between these factors is complex, though targeting sex differences in the pathophysiology of PD may open new avenues of investigation and possibly the development of sex-specific treatments.
I feel like my Parkinson’s disease symptoms fluctuate
with my period - could that be true?
Caring for women with Parkinson’s disease must include acknowledgement of their “unique hormonal life stages.” Women often report worsening of motor symptoms in the premenstrual phase. In fact, an advocate driven survey of 200 women with PD corroborated this phenomenon.
The premenstrual estrogen drop is thought to be responsible for this effect with conflicting reports of the benefit from taking extra levodopa during this time period (as a symptomatic approach). This area is largely unexplored .
How about pregnancy in Parkinson’s?
Although Parkinson’s disease in general is diagnosed at an older age, approximately 5% of women are diagnosed before age 40. This group of young onset PD patients (YOPD) includes women considering a pregnancy (after diagnosis) and who may be having ongoing menses and associated hormonal fluctuations— which may need to be managed by contraception or hormonal regulation. With increasing maternal age and increasing incidence of PD, especially YOPD worldwide, pregnancy in women with PD will be more common in the future. PD symptoms have been reported to worsen during pregnancy and the post-partum period. The pathophysiology of these changes are not well understood. Levodopa alone is the most reported treatment utilized in PD during pregnancy— and levodopa does not seem to result in an increased risk of birth defects or adverse outcomes. Amantadine, is a known teratogen and should not be used in pregnancy. However, there are no evidence-based guidelines on the management of PD during pregnancy and there is a paucity of literature on maternal safety— especially around c-sections, obstetrical anesthesia, post-partum depression and fetal outcomes.
How about menopause? I feel like my PD symptoms
worsened with menopause.
Women with Parkinson’s disease may also report pre-menopausal worsening of symptoms—this is thought to be due to a drop in estrogen. Once women have been diagnosed with PD, the question arises as to whether HRT could be beneficial in treating fluctuations in PD symptoms during peri-menopause and post-menopause. There has been much confusion about whether and when to start HRT. Neurologists and gynecologist should better collaborate in research (to do the right studies and ask the right questions)— as well as creating closer collaborations for the clinical care of women with PD— during all these hormonal transitions. Finally, to properly advise and to guide women who are considering a pregnancy in the future, we recommend formation of an international prospective registry.
To read more books and articles by Michael S. Okun MD check on Twitter @MichaelOkun and these websites with blogs and information on his books and http://parkinsonsecrets.com/ #Livingwith Parkinson’s #EndingPD #Parkinsonsecrets #LessonsFromTheBedside
He also serves as the Medical Advisor for the Parkinson’s Foundation.
To see more on Dr. Indu Subramanian she does live interviews of experts in Parkinson’s for the PMD Alliance.
The blog artist is Jonny Acheson.