Comparison of Fundamental Frequency in Postmenopausal Women Who Are Treated With Hormone Replacement Therapy vs Those Who Are Not: A Systematic Review and Meta-analysis

IMPORTANCE: Hormonal changes during menopause have been associated with significant changes in voice. Although hormone replacement therapy (HRT) is used primarily to manage systemic symptoms of menopause, its association with voice in postmenopausal women has not been adequately investigated by large-scale studies. OBJECTIVE: To compare fundamental frequency between postmenopausal women who used HRT and those who did not use HRT. DATA SOURCES: PubMed, Ovid MEDLINE, CINAHL, Cochrane EBM Reviews, and Embase were searched from 1946 to February 19, 2020. STUDY SELECTION: Studies included in the final review were those in English that compared voice outcomes in postmenopausal women who were or were not receiving HRT for treatment of climacteric symptoms associated with menopause. DATA EXTRACTION AND SYNTHESIS: The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data extraction was performed by 2 independent investigators. Study quality was assessed using a validated quality tool. Whenever possible, data were pooled using random-effects meta-analysis. MAIN OUTCOMES AND MEASURES: The primary outcome was the difference in speaking fundamental frequency (F0) between HRT users and nonusers. Subgroup analysis of the primary outcome was based on body mass index (BMI) using a cutoff value of 25. A BMI of 18.5 to 24.9 is considered normal, and a BMI of at least 25 is considered overweight. Secondary outcomes included other objective measurements of voice, including jitter and shimmer. RESULTS: A total of 937 records were screened, 18 full texts were assessed, and 11 studies were included in the final review. All 11 studies were case-control studies and were rated from fair to good quality based on the Newcastle-Ottawa Scale. A total of 5 studies including 154 participants who received HRT and 154 controls were used for meta-analysis. The mean (SD) F0 was 185.9 (8.6) Hz for HRT users compared with 174.6 (6.6) Hz for nonusers. Hormone replacement therapy was associated with a higher mean F0 by a difference of 11.85 Hz (95% CI, 7.35-16.36 Hz). Subgroup analysis showed that the change in F0 was significant in postmenopausal women with a normal body mass index (mean difference, 13.47 Hz; 95% CI, 8.48-18.46 Hz) but not in those with a high body mass index. CONCLUSIONS AND RELEVANCE: Existing evidence suggests that HRT is associated with a higher F0 in postmenopausal women. The effectiveness of the treatment appeared to be more pronounced in women with a normal body mass index.