Objective: The role of estrogen in dopaminergic pathways and the premenstrual worsening of parkinsonian symptoms.

Background: Female sex hormones, during the menstrual cycle, could influence behaviour and peripheral nociception in the so-called Premenstrual Syndrome, but also there is a debate about their effects on central neurotransmission. Some authors suggest that fluctuating female sex hormones during the menstrual cycle do not significantly alter central dopaminergic neurotransmission, while others proposed that estrogen fluctuations reduces the dopaminergic neurotransmission.

Method: Out of our Movement Disorder database we selected 11 women who had regular menstrual cycles, within the range of 24-35 days. None of the women was pregnant or had taken an oral contraceptive pill prior to the observation. The duration of the observation was 4 months, and 3 full menstrual cycles UPDRS I-III subscale ratings were performed every week by one expert neurologist unaware of the cycle phase of the women. The women had to complete every 3 days a self-rating chart to rule out a diagnosis of PMS. The different phases of the cycle were defined as follows: menstruate- (days 2-6), follicular- (days 9-13), early luteal- (days 16-20), and late luteal phase (days 24-30).

Results: 9 patients completed the observations, 1 patient discontinued the study because of loss of follow-up, and 1 patient was not taken into account at the final evaluation because of irregular menstrual cycles. 6 patients affected by young onset PD and in childbearing age 32-42 years old (38.5±3.6, mean ± SD) and 3 patients in the premenopausal period 48-51 years old (51.0±3) were considered for the final results. All but one (pat. DA) were on L-Dopa and/or dopamine agonist therapy. Changes in UPDRS during premenstrual period are described in Table 1.

Conclusion: Our results confirm the role of estrogen in dopaminergic pathways, and the abrupt reduction of estrogen levels during the perimenstrual period may contribute to reduced responsiveness to dopaminergic treatment during menses.

Worsening of parkinsonian symptoms seems to be related to estrogen levels, particularly its nadir level, rather than a premenstrual syndrome.

Estrogen impacts nigrostriatal functions at multiple levels, including synthesis, release, reuptake, and dopamine receptor expression in the basal ganglia. A high level of estrogen appears to be neuroprotective, but further investigations are required.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/premenstrual-worsening-of-updrs-motor-scale-in-women-affected-by-parkinsons-disease/