Bone mineral density in women aged 40–49 years using depot-medroxyprogesterone acetate, norethisterone enanthate or combined oral contraceptives for contraception

Abstract

Most studies show that depot-medroxyprogesterone acetate (DMPA) has a negative effect on bone mass. There are conflicting reports with respect to recovery of bone mass with long-term use of DMPA. No information is available on the effect of norethisterone enanthate (NET-EN) on bone mass, and combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass. The aim of this study was to investigate bone mineral density (BMD) in older women (40–49 years) in relation to use of DMPA, NET-EN and COCs for at least 12 months preceding recruitment into the study.

One-hundred twenty-seven users of DMPA, 102 NET-EN users and 106 COC users were compared to 161 nonuser controls. Bone mineral density was measured at the distal radius and midshaft of the ulna using dual X-ray absorptiometry.

There was no significant difference in BMD between the four contraceptive user groups (p=.26) with and without adjustment for age. Although a small decrease in BMD was noted in the age range of 40–49 years, this was not statistically significant (p=.7). The BMD was found to be significantly associated with body mass index (BMI) (p≤.0001) at both measurement sites, with an increase of one unit of BMI translating to an increase of 0.0044 g/cm² in radius BMD. Follicle-stimulating hormone (FSH) level ≥25.8 mIU/mL was associated with a decrease of 0.017 g/cm² in radius BMD relative to women with FSH <25.8 mIU/mL. Significant interaction between FSH and BMI in their effect on BMD was observed (p=.006). This study found no evidence that long-term use of DMPA, NET-EN and COCs affects BMD in this population.

Introduction

Cross-sectional studies undertaken to investigate the effect of hormonal contraceptives on bone mineral density (BMD) have produced conflicting reports [1], [2], [3], [4], [5], [6], [7]. Most have indicated that depot-medroxyprogesterone acetate (DMPA) has a negative effect on bone mass [1], [2], [3], [4], [5], and some have shown minimal or no effect [6], [7], [8]. The loss of BMD in the case of DMPA has been associated with estrogen deficiency [9]. Some of these studies show that these negative changes are reversible and there is a return to pre-use levels on discontinuation of the method [1], [10]. In addition, there has been evidence of recovery of BMD in long-term users [1], [6], [11]. There is no information available on the effect of norethisterone enanthate (NET-EN) on bone mass; however, published studies on norethisterone (NET) have shown a positive effect on BMD [12], [13], [14]. Combined oral contraceptives (COCs) have not been found to be associated with loss of bone mass [15], [16], with some studies indicating that COCs are bone-sparing [16], [17].

Few studies have investigated the effect of hormonal contraceptives on BMD in premenopausal long-term users of hormonal methods in their 40s, and none have investigated the effect of NET-EN on BMD.

Depot-medroxyprogesterone acetate and norethisterone enanthate are effective contraceptives with low failure rates [18]. In South Africa, hormonal injectable contraceptive use is high, with about 60% of Black African women practicing contraception using either DMPA or NET-EN [19]. Of the two available injections, older women mainly use DMPA and often continue to use this method into their late 40s. Use of COCs is lower with the method predominantly used by white and Asian women. As menopause is known to be associated with bone loss [20], it would be important to know if hormonal methods of contraception could further contribute to bone loss in older women.

The aim of this study was to determine if long-term use of hormonal contraceptives (COCs, DMPA and NET-EN) is associated with change in bone mass in women aged 40–49 years.