Effect of Menopausal Status on Chemotherapy-Induced Peripheral Neuropathy: Single-Institution Retrospective Audit

Abstract

Abstract Introduction Paclitaxel can cause peripheral neuropathy in up to 60% of patients. Chemotherapy-induced peripheral neuropathy (CIPN) compromises quality of life and often leads to dose reduction or discontinuation of lifesaving chemotherapy. Preclinical models have suggested the possible neuroprotective effect of progesterone through remyelination and other mechanisms. Objectives The aim of this study was to evaluate the incidence of CIPN for different menopausal status. Materials and Methods We evaluated the effect of menopausal status, as a surrogate for circulating progesterone levels, on the risk of developing paclitaxel-induced peripheral neuropathy, in an audit of breast cancer patients. Data on CIPN (by clinical history and examination) and other variables were collected from the case charts of patients who had received paclitaxel-based chemotherapy for breast cancer at our institution. Results Five hundred and fifty women were treated with either neoadjuvant or adjuvant paclitaxel in this period. Of these, 262 (47.6%) women were premenopausal, 49 (8.9%) were perimenopausal, and 239 (43.5%) were postmenopausal at the time of diagnosis. Forty-five (8.1%) women had pre-existing diabetes mellitus. Two hundred and fifty-six (82.31%) developed chemotherapy-induced amenorrhea (CIA).CIPN was seen in 32.7% of women who continued to be premenopausal after receiving chemotherapy and 62.3% of postmenopausal women. Thirty-five (77.8%) out of forty-five diabetic women developed CIPN. On a multivariate logistic regression model, pre-existing diabetes mellitus (risk ratio [RR] = 2.64, 95% confidence interval [CI]: 1.26–5.52, p = 0.009), postmenopausal (RR = 2.84, 95% CI = 1.48–5.45, p = 0.002), and CIA status (RR = 2.17, 95% CI = 1.14–4.12, p = 0.018) were significantly associated with the development of CIPN. Number of cycles did not appear to have an impact (p= 0.819). Conclusions Postmenopausal status was independently associated with higher incidence of CIPN. One of the possible mechanisms could be lower circulating progesterone levels in these patients. A randomized controlled trial (CTRI/2015/11/006381) is ongoing to test this hypothesis.