Incidence of abnormal uterine bleeding and endometrial hyperplasia in postmenopausal women treated with Pellet Hormonal Therapy

Objective: The objective of this study was to assess the incidence of abnormal uterine bleeding (AUB) and endometrial hyperplasia in postmenopausal women treated with non-FDA approved Pellet Hormonal Therapy (PHT) while compared with FDA approved Hormonal Therapy (FHT). Design: A retrospective cohort study was designed to compare two cohorts (PHT vs. FHT). A total of 522 postmenopausal women with menopausal symptoms were identified from the Reading Hospital Electronic Medical Record System through pharmacy coding, including 367 on PHT (estradiol [E2, 6-37.5mg] and/or testosterone [T,12-137.5 mg] pellets) and 155 on FHT. Data on demographics, initial menopausal symptoms (i.e. hot flash, vaginal dryness, decreased libido), side effects (i.e. AUB, mood swing, anxiety, breast tenderness, change in hair pattern, acne, weight gain), and treatment duration were extracted from medical records. Chi-Square test was applied to assess the difference in incidence of side effects between the two cohorts, and a multiple logistic regression was fit with covariates (HT cohort, age at the initiation of HT, Body Mass Index, duration of HT), to assess risk profile of the individual covariate. Results: Women on PHT (n=367) were significantly younger than those on FHT (n=155), with mean age (SD) of 51.04 (7.52) and 60.61 (9.56) years, respectively (p\u3c.0001). The incidence of side effects was significantly higher in PHT while compared with FHT (179 [49.5%] vs. 23 [15.3%], p\u3c.0001, odds ratio [95% CI] =5.92[3.42-10.25]). A total of 91 (58.7%) women on FHT had a hysterectomy prior to the initiation of HT, which was significantly higher than the 151 (41.4%) on PHT (p=0.0003). When examining 276 women with an intact uterus prior to HT initiation, mean (SD) duration of HT treatment in years were significantly longer in PHT group (3.11 [1.64] vs. 2.15 [2.22], p=.0023). During the treatment, 59.4% (127/214) on PHT vs. 19.4% (12/62) on FHT had at least one episode of AUB (p\u3c.0001, odds ratio [95% CI] =7.15[3.00-17.04]). Of those, 54 (27%) and 5 (7.8%) had a hysterectomy while on PHT and FHT respectively (p=.0013, odds ratio [95% CI] =3.49[1.22-9.99]), and 87(41.8%) in PHT vs. 10 (16.4%) in FHT had endometrial pathology available either from endometrial biopsy or hysterectomy. No endometrial cancer was identified in either group. There was no significant difference in incidence of endometrial hyperplasia between the two cohorts (22[25.9%] vs. 4[40.0%]), with 3(14%) in PHT vs. 0 in FHT being diagnosed with endometrial hyperplasia with atypia. A total of 201 women on PHT had lab monitoring data available, abnormal E2 and T level were detected in 52 (25.9%) and 133 (66.2%) women, respectively, who subsequently required dose adjustment. Conclusion: When compared with women on FHT, women on PHT had a significantly higher incidence of AUB and hysterectomy. It may be difficult to assess difference in incidence of endometrial hyperplasia due to relatively rare outcome and short durations of HT treatment in our study. Large scale prospective clinical trials are warranted to further investigate the safety of PHT for treating menopausal symptoms