Menopausal hormone therapy and the incidence of carpal tunnel syndrome in postmenopausal women: Findings from the Women's Health Initiative

Abstract

Importance: Carpal tunnel syndrome (CTS) is a common and debilitating condition that commonly affects postmenopausal women.

Objective: To determine the effect of menopausal hormone therapy (HT) in healthy postmenopausal women on CTS risk.

Design: We conducted a secondary analysis of the Women's Health Initiative's (WHI) HT trials linked to Medicare claims data. Separate intention-to-treat analyses were performed for the two trials; the conjugated equine estrogens alone (CEE alone) and the trial of CEE plus medroxyprogesterone acetate (MPA) trial. (ClinicalTrials.gov, NCT number): NCT00000611.

Setting: Two randomized, double-blind, placebo-controlled trials conducted at 40 US clinical centers.

Participants: The sample size included in the analysis was 16,053 community-dwelling women aged ≥65 years at study entry or those who later aged into Medicare eligibility, and who were enrolled in Medicare (including Part A and/or Part B coverage).

Intervention: Women with hysterectomy were randomized to 0.625 mg/d of conjugated equine estrogens (CEE) or placebo (n = 8376). Women without hysterectomy were randomized to estrogen plus progestin (E+P), given as CEE plus 2.5 mg/d of medroxyprogesterone acetate (n = 14203).

Main outcome(s): The primary outcome was incident CTS and the secondary outcome was therapeutic CTS procedure occurring during the intervention phases of the trials.

Results: A total of 16,053 women were randomized in both trials. During mean follow up of 4.5 ± 2.8 years in the CEE trial (n = 6,833), there were 203 incident CTS cases in the intervention and 262 incident CTS cases in the placebo group (HR, 0.78; 95% CI, 0.65-0.94; P = 0.009). The CEE+MPA trial (n = 9,220) followed participants for a mean of 3.7 ± 2.3 years. There were 173 incident CTS cases in the intervention compared to 203 cases in the placebo group (HR, 0.80, 95% CI, 0.65-0.97; P = 0.027).

Conclusions: These findings suggest a protective effect of menopausal HT on the incidence of CTS among postmenopausal women. A potential therapeutic role for other forms of estrogen therapy in the management of CTS warrants future research.

Conflict of interest statement

Only one co-author (Andrew M. Kauntiz) has competing interest to declare. He is a consultant that sits on the advisory board of “Allergan, Bayer, Mithra, Shionogi; and his institution (University of Florida) receives research support from: “Bayer, TherapeuticsMD, Mithra”. However, this does not alter our adherence to PLOS ONE policies on sharing data and materials.” (as detailed online in our guide for authors http://journals.plos.org/plosone/s/competing-interests). All other coauthors have no competing interests to declare.

Figures

Fig 1. Flowchart of the woman study enrollment.

Individuals were excluded prior to randomization for safety reasons such as history of breast cancer (4.5%), or clinic staff impression that a woman was not a good candidate for the study (4.8%). Some women were not included in the trial if the stratum was closed (4.6%). The majority of exclusions were due to lack of interest or no informed consent for the estrogen therapy component of the Women’s Heath Initiative (81.2%). CEE, conjugated equine estrogens; MPA, medroxyprogesterone acetate.

Fig 2. Cumulative hazard curves for carpal tunnel syndrome outcomes in the women’s health initiative (whi) estrogen alone and the estrogen and progestin trials during the intervention periods1.

Cumulative hazard curves for CTS diagnosis in the Women’s Health Initiative CEE (panel A) and the CEE+MPA (panel B) trials during the intervention periods. Comparable plots are shown for CTS procedure in the CEE (panel C) and the CEE+MPA (panel D). The intervention reduces the cumulative hazard of CTS cases by 22% in the CEE trial and by 20% in the CEE+MPA trial. A similar trend is seen for CTS procedures but it was not statistically significant. Cox proportional hazard models were used where time zero started when each participant’s Medicare coverage started. CEE, conjugated equine estrogens; MPA, medroxyprogesterone acetate; CI, confidence interval; HR, hazard ratio. 1Hazard ratios (HR) and 95% confidence intervals (CI) estimated from Cox proportional hazards models; p-values based on Wald Chi-square statistics.

Fig 3. Subgroup analysis for development of carpal tunnel syndrome diagnosis by demographic and medical history.

Subgroup analysis for development of CTS. Point estimates represent hazard ratios of the intervention compared to placebo and the whiskers are 95% confidence limits. BMI, Body Mass Index. There was no statistically significant interaction. The P values shown have not been adjusted for multiple comparisons.