Effect of hormone replacement therapy on uterine fibroids in postmenopausal women—a 3-year study

Abstract

Objective: The aim of this prospective 3-year clinical study was to examine the effect of hormone replacement therapy (HRT) on uterine fibroid growth among postmenopausal women. Methods: Thirty-seven postmenopausal women with uterine solitary fibroids were recruited randomly for HRT in a 3-year program. All participants received 0.625 mg conjugated equine estrogen (CEE) and 5 mg medroxyprogesterone (MPA) daily. Fibroid volume was measured by transvaginal ultrasonography at baseline and then at 12-month intervals for 3 times. Clinically, significant fibroid growth was defined as an increase in volume of more than 25% compared with baseline. Also, 35 postmenopausal women with uterine fibroid were studied as control who did not receive HRT during the study period. Results: Fibroid volume had increased significantly after 1 year both in HRT users and non-users. These increases continued to the second year significantly in HRT users but not in non-users. However, the volumes declined significantly at the third year to similar levels as those measured at baseline in control. In HRT users, fibroid volume though significantly increased at the third year (vs. baseline) but declined insignificantly in comparison with the second year. Clinically, at end of the third year study, one of 34 and three of 34 women increased fibroid volume over 25% compared with baseline in HRT non-users and users, respectively. Conclusions: HRT does increase uterine fibroid volume statistically. However, its effect appears in the first 2 years of use. The increased fibroid volume begins to decline at the third year both in HRT users and non-users. Clinically, the increased effect of HRT on uterine fibroid of postmenopausal women should be not over-emphasized at least for 3 years of usage.

Introduction

Although the exact stimulus for growth of uterine fibroids remains undetermined, sex steroids are strongly associated with development of fibroids. Several findings support this hypothesis: (1) fibroids are rare before menarche and regress after the menopause; (2) fibroids reduce in size with GnRH agonists through their impact on reproductive axis [1]; (3) the reactivity of fibroids is related to the presence of receptors for estrogens and progestins [2]; and (4) mitoses are increased in fibroids during the luteal phase of the menstrual cycle [3]. However, there is controversy concerning the natural history of fibroids during pregnancy [4], [5], [6]: it has been reported that fibroids increase in volume by 31.6% during pregnancy, most markedly during the first trimester [7], while another study indicated that myomas did not increase in size during pregnancy [8].

The benefits of hormone replacement therapy (HRT) in the postmenopause for prevention of osteoporosis, cardiovascular disease and the onset of Alzheimer's dementia have been well documented [9], [10], [11]. Despite these benefits, compliance with HRT remains less than optimal owing to fears concerning adverse effects such as tumor growth, weight gain, irregular bleeding and the recurrence of premenstrual tension. Though breast cancer is a major concern, the high prevalence of uterine fibroids in women is the biggest factor leading to reluctance to prescribe HRT for postmenopausal women.