Sex Differences, Hormonal Influences, and Caregiving Burden in Women With Parkinson Disease

In recognition of Parkinson’s Disease Awareness Month, held annual in April, growing attention has been placed on understanding sex-specific differences in Parkinson disease (PD), particularly among women. Although studies have shown that PD is more prevalent in men, research describes that women experience distinct clinical patterns, including differences in motor complications, nonmotor symptoms, and quality of life. Evidence suggests that hormonal factors, including the potential neuroprotective effects of estrogen and changes associated with menopause, may also contribute to variations in disease risk, symptom expression, and overall trajectory.

Despite these differences, women remain underrepresented in clinical trials, potentially limiting the evidence base needed to inform sex-specific treatment strategies and counseling. This gap has clinical implications for understanding pharmacologic responses, hormone-related influences, and outcomes that may be particularly meaningful to women living with the movement disorder. Additionally, women with PD can often face unique social challenges, including a disproportionate burden of caregiving responsibilities, which may further affect their experience and management with the condition.

To further explore these considerations, NeurologyLive^® spoke with PD experts Sameea Husain, DO, director of movement disorder neurology at Marcus Neuroscience Institute, a part of Baptist Health South Florida, and Sarah Marmol, MD, a neurologist specializing in movement disorders at Miami Neuroscience Institute. In this Q&A, the duo discussed the current understanding of hormonal influences, clinical differences between men and women, and the broader implications of these gaps in research and care. Their clinical perspectives highlight the importance of a more individualized, gender-informed approach to the management of PD.

NeurologyLive: How do hormonal transitions appear to influence the onset or progression of PD in women?

Sameea Husain, DO: Sex hormones have been implicated in neurite outgrowth, synaptogenesis, dendritic branching, myelination and other important mechanisms of neural plasticity. Many brain regions have been demonstrated to express high densities for estrogen- and progesterone receptors, such as the amygdala, the hypothalamus, and the hippocampus. These structures are not where dopaminergic degeneration is occurring in PD which implies that hormonal transitions in women are less likely to influence the onset or progression of PD however they can be implicated in how a women’s brain changes with aging as these hormone levels drop.

Sarah Marmol, MD: Women have a lower lifetime risk of PD than men, a difference widely attributed—at least in part—to estrogen’s neuroprotective effects on dopaminergic pathways. Estrogen modulates dopamine synthesis, release, and receptor sensitivity and has anti‑inflammatory and antioxidant effects, all relevant to PD pathophysiology.^1,2

The menopausal transition represents a critical inflection point. Large clinical reviews show that:

• Earlier menopause, surgical menopause, and shorter lifetime estrogen exposure are associated with increased PD risk and sometimes earlier onset.^3,4
• Postmenopausal women with higher residual estradiol levels tend to have milder motor symptoms and lower dopaminergic medication requirements.⁵

Biomarker studies further suggest that postmenopausal hormonal changes may influence cognitive trajectory and co‑pathologies (e.g., amyloid and tau markers), not just motor severity.⁵

Survey‑based and qualitative research shows that many pre‑ and perimenopausal women experience cyclic motor and non‑motor symptom fluctuations and reduced medication efficacy during hormonal transitions, yet these issues are rarely proactively addressed in clinical encounters.⁶

️Importantly, evidence on hormone replacement therapy (HRT) remains mixed. While some observational studies suggest reduced PD risk or motor benefit, inconsistencies in timing, formulation, and patient selection preclude firm clinical recommendations.^3,7

How does the clinical presentation or trajectory of PD differ in women compared to men?

Sameea Husain, DO: The prevalence of PD is higher in men than in women. This discrepancy suggests the potential existence of sex-associated factors that modify the disease process. Identifying the interplay between sex and PD has the potential to assist the development of disease-modifying therapy, inform patient management strategies, and allow the planning of more efficient clinical trials. Research indicates that meant are more likely to experience akinesia/rigid features, cognitive impairment, daytime sleepiness and REM sleep behavior disorder more frequently than women. In contrast, women her more likely to experience anxiety disorder/depression dyskinesias.

Sarah Marmol, MD: How PD differs clinically in women compared to men:

• Men have a 1.5–3× higher incidence of PD and tend to be diagnosed slightly earlier.¹
• Women are often diagnosed later and with greater reported disability, despite similar disease duration—suggesting diagnostic delay or underrecognition.⁸

Consistent findings across reviews and meta‑analyses include:

• Women experience more motor complications, particularly levodopa‑induced dyskinesias and motor fluctuations.²
• Women report greater non‑motor symptom burden, especially depression, anxiety, fatigue, and pain.⁹
• Men are more likely to develop cognitive impairment, gait dysfunction, and postural instability.²

Large cohort studies show that disease progression rates are broadly similar by sex, but quality of life and perceived disability are worse in women, driven in part by mood symptoms and social context rather than motor severity alone.¹

Women have historically been underrepresented in PD clinical trials, what do you see as the most consequential gaps this has created in how we treat or counsel female patients today?

Sameea Husain, DO: Women, and specifically women of color, are underrepresented in clinical trials, limiting biological understanding and contributing to health inequities and social injustice. These gaps limit the understanding of sex-based differences in disease expression, progression, and therapeutic response, thereby limiting precision medicine.

Sarah Marmol, MD: Women remain consistently underrepresented in PD trials, especially in studies of advanced therapies such as infusion systems and device‑based treatments.¹⁰

Key gaps this has created:

1. Uncertain dosing and side‑effect profiles: Women have different pharmacokinetics, body composition, and dopamine sensitivity, yet sex‑stratified analyses are rarely reported, limiting confidence in dosing recommendations.^10,11

2. Inadequate guidance on hormone‑drug interactions: Almost no trials account for menopausal status, HRT, or cyclic hormonal effects—leaving clinicians without evidence‑based counseling tools for symptoms that women clearly report.^6,12

3. Delayed recognition of sex‑specific outcomes: Outcomes meaningful to women—fatigue, mood, caregiving capacity, social participation—are less likely to be primary endpoints, skewing our understanding of “treatment success”.¹²

4. Equity and trust issues: Women’s underrepresentation reinforces disparities in access to advanced therapies and undermines patient trust in research relevance.^10,13

Given that women with PD also disproportionately shoulder caregiving responsibilities, how do you approach conversations about that dual burden with patients?

Sameea Husain, DO: When discussing the dual burden of caregiving and PD with patients, it is essential to approach the conversation with empathy and understanding. Caregivers often face significant emotional, physical, and financial strain, which can impact their well-being and the quality of care they provide. It is crucial to listen to the caregivers' concerns and recognize the challenges they face.

• Acknowledge the Strain: Recognize that caregivers are often burdened with the responsibility of caring for someone with PD, which can lead to increased stress and burnout.
• Encourage Support: Suggest exploring support systems, such as support groups, therapy, or respite care, to help caregivers manage their responsibilities.
• Educate on Caregiver Responsibilities: Inform patients about the various roles caregivers can take, such as assisting with daily activities, medication management, and reporting new issues to the medical team.
• Promote Gender-Sensitive Care: Address the gender-related differences in caregiving and the impact of gender norms and stereotypes on patients' well-being and care access.
• Encourage Collaboration: Foster collaboration between caregivers and healthcare providers to ensure that the needs of both the patient and the caregiver are met.

By approaching conversations about the dual burden with care and sensitivity, healthcare providers can better support both the patient and the caregiver, ultimately improving the quality of care and the overall well-being of those affected by Parkinson's disease.

Sarah Marmol, MD: Women with PD often continue to shoulder caregiving roles—for spouses, parents, or grandchildren—despite their own progressive disability. Female gender itself is a risk factor for higher caregiver burden and worse health outcomes in PD contexts.¹⁴

Evidence from qualitative and mixed‑methods studies supports several key principles:

1. Normalize and explicitly name the dual role: Many women minimize their strain. Naming caregiving as a clinical issue opens the door to intervention.¹⁵

2. Screen early and repeatedly: Care burden, depression, and physical strain accumulate over time; proactive screening is associated with better caregiver health outcomes.¹⁶

3. Link symptom management to role sustainability: Framing optimized symptom control as a way to preserve independence and caregiving capacity aligns treatment goals with patients’ values.¹⁷

4. Validate identity shifts: Qualitative studies highlight grief around loss of role balance and autonomy. Validation alone can meaningfully reduce distress.¹⁵

5. Offer concrete supports: Education, respite resources, social work involvement, and caregiver‑specific care plans reduce burden and downstream morbidity.^16,18

Transcript edited for clarity. Click here for more coverage on Parkinson disease.

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