Sex Disparities in Autonomic Symptom Treatment in Parkinson's Disease

Emerging data suggest sex differences in Parkinson's disease (PD) management. ¹ , ² Possible reasons include provider biases and differences in symptom severity and access to care. Identifying other aspects of PD where sex disparities exist will help optimize outcomes. Symptoms of dysautonomia in PD impact quality of life. ³ Sex differences in autonomic symptoms in PD exist, ² but whether this extends to recognition and treatment is unknown. To address this gap in knowledge, we examined potential sex disparities in autonomic symptom treatment in patients with PD.

The data used for this analysis were from the Parkinson's Progression Markers Initiative, a multicenter study aimed at identifying PD progression biomarkers. Institutional review board approval was obtained at each site, and written informed consent was obtained from each participant (see Supplementary Methods in Appendix S1 for detailed methodology). We examined autonomic symptom severity and treatment at the year‐5 Parkinson's Progression Markers Initiative visit, when participants had 5 to 7 years of disease and a significant proportion were expected to have dysautonomia. Autonomic symptoms were assessed using the Scales for Outcomes in Parkinson's Disease–Autonomic (SCOPA‐AUT). To assess autonomic symptom treatment, medication logs were reviewed and data regarding treatment extracted. The participants were classified as receiving medications for each of the following, grouped according to SCOPA‐AUT subscore: gastrointestinal, urinary, cardiovascular, sexual.

A total of 308 participants with complete year‐5 SCOPA‐AUT scores were included; 2 participants with an indwelling foley catheter were excluded. Age, mean MDS‐UPDRS scores, and levodopa equivalent dose were significantly higher in men (Supplementary Table 1 in Appendix). SCOPA‐AUT total urinary subscore was not different between men and women, although on individual items, women were more likely to have urinary incontinence and men incomplete bladder emptying and weak urinary stream (Supplementary Table 2 in Appendix S1). Sexual subscore was higher in men, although women were more likely to have difficulty with orgasm (Supplementary Table 2 in Appendix S1). Men were more likely to receive a medication for urinary or sexual symptom treatment (Table 1). The odds of receiving treatment for urinary symptoms remained higher in men when controlling for age and SCOPA‐AUT urinary subscore (odds ratio, 3.565; P = 0.003; 95% confidence interval, 1.528–8.318).

TABLE 1.

Autonomic symptom treatment among sexes

Autonomic Symptom Category	Medications Included	Number of Men (%)	Number of Women (%)	P Value
Gastrointestinal	Antacids, docusate, domperidone, fiber, histamine antagonists, lactulose, linaclotide, lubiprostone, metoclopramide, ondansetron, polyethylene glycol, probiotics, prochlorperazine, proton pump inhibitors	85 (41.67)	45 (43.27)	0.073 a
Urinary	Alpha antagonists, anticholinergic agents, botulinum toxin, desmopressin, saw palmetto	47 (23.04)	7 (6.73)	<0.001 a
Cardiovascular	Droxidopa, fludrocortisone, midodrine, pyridostigmine, salt tablets	7 (3.43)	1 (0.96)	0.275 b
Sexual	Phosphodiesterase inhibitors, estrogen cream, oral estrogen, vaginal lubricant	32 (15.69)	0 (0.00)	<0.001 b

^aChi‐squared analysis.

^bFisher exact test.

One potential explanation for the disparity in urinary symptom treatment is that men are more likely to be screened for urinary dysfunction given concerns for prostate hypertrophy/cancer. Alternatively, a reported barrier to the management of female urinary dysfunction includes an assumption by the patient that it is part of normal aging. ⁴ Sexual dysfunction in women may also be underdetected/undertreated. ⁵ Women are less likely to receive/maintain PD specialty care, ¹ potentially contributing to treatment disparities as well. Limitations of this study include the possibility of excluding subjects with severe disease; only those completing the year‐5 visit were included. It is also difficult to compare sexual subscores because of different symptoms and because more women responded not applicable. Lastly, we did not assess for non‐PD‐related causes of autonomic symptoms; differences in individual urinary subscore items may reflect sex‐specific pathology such as pelvic floor dysfunction and prostate hypertrophy.

Our results indicate that despite no difference in overall urinary symptom prevalence, women were less likely to be treated for urinary dysfunction than men. Future studies should evaluate causes for this disparity.

Author Roles

(1) Research Project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and critique.

C.M.P.: 1B, 1C, 2A, 2B, 3A

K.A.E.: 1B, 1C

L.M.C.: 1A, 2A, 2C, 3B

Disclosures

Ethical Compliance Statement: Each Parkinson's Progression Markers Initiative site received approval from an ethical standards committee on human experimentation before study initiation and obtained written informed consent from each study participant. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines.

Funding Sources and Conflicts of Interest: Parkinson's Progression Markers Initiative is funded by the Michael J Fox Foundation for Parkinson's Research and funding partners, including AbbVie, Allergan, Avid Radiopharmaceuticals, Biogen, BioLegend, Bristol‐Myers Squibb, Celgene, Denali, GE Healthcare, Genentech, GlaxoSmithKline, Lilly, Lundbeck, Merck, Meso Scale Discovery, Pfizer, Piramal, Prevail Therapeutics, Roche, Sanofi Genzyme, Servier, Takeda, Teva, UCB, Verily, Voyager Therapeutics, and Golub Capital. The authors declare that there are no conflicts of interest relevant to this work.

Financial Disclosures for the Previous 12 Months: The authors declare that there are no additional disclosures to report.

Supporting information

Appendix S1. Supporting information.