How well is the female population represented in clinical trials with infusion therapies for Parkinson's disease? A systematic review and metanalysis

Eur J Neurol. 2025 Jan;32(1):e70024. doi: 10.1111/ene.70024.

Abstract

Background: Parkinson's disease (PD) is a neurodegenerative disorder affecting both sexes, but differences exist between male and female in clinical manifestations, functional impact of symptoms and hormonal influences. Therefore, representativeness of females in PD trials indirectly determines the external validity of the clinical research in this field.

Objective: To estimate the representativeness of female in infusion therapy trials for advanced PD.

Methods: PubMed and EMBASE databases were searched (1980 to September 2023), along with congress abstracts, to identify controlled clinical trials and large non-controlled studies on infusion therapies in PD enrolling >100 patients. Random-effect meta-analysis was conducted to estimate mean pooled prevalence of females included in the studies. Subgroup analyses were conducted accordingly to study design and intervention.

Results: We included 15 studies (six studies on levodopa-carbidopa intestinal gel, six on subcutaneous levodopa, two on subcutaneous apomorphine, and one on levodopa-carbidopa-entacapone intestinal gel). Sex was not a randomisation stratification factor in any of these studies. Only one study explored differences in the outcome estimated according to sex. Overall, the proportion of female included was 38% (95% CI:33%-43%; I2 = 74%), without differences between studies assessing different type of interventions (p = 0.72) or between study design (p = 0.35). In two studies, females represented the majority of included patients.

Conclusion: Female with advanced PD are underrepresented in infusion therapy trials. Most trials have overlooked sex-based biological differences that can impact clinical and functional outcomes, raising concerns about the generalizability of these findings to real-world contexts.

Keywords: Parkinson's disease; female; gender equity; infusion pumps.

Publication types

  • Systematic Review
  • Meta-Analysis
  • Review

MeSH terms

  • Antiparkinson Agents* / administration & dosage
  • Antiparkinson Agents* / therapeutic use
  • Apomorphine / administration & dosage
  • Carbidopa / administration & dosage
  • Clinical Trials as Topic
  • Drug Combinations
  • Female
  • Humans
  • Levodopa / administration & dosage
  • Levodopa / therapeutic use
  • Male
  • Parkinson Disease* / drug therapy
  • Sex Factors

Substances

  • Antiparkinson Agents
  • Levodopa
  • carbidopa, levodopa drug combination
  • Apomorphine
  • Drug Combinations
  • Carbidopa