Elsevier

Contraception

Volume 74, Issue 4, October 2006, Pages 297-302
Contraception

Original research article
Effects of the long-term use of depot medroxyprogesterone acetate as hormonal contraceptive on bone mineral density and biochemical markers of bone remodeling

https://doi.org/10.1016/j.contraception.2006.04.003Get rights and content

Abstract

Purpose and Method

Our objective is to evaluate the effects of the long-term use of depot medroxyprogesterone acetate (DMPA) as a method of contraception on bone mineral density (BMD) and bone remodeling. Forty women (21–44 years old) who used DMPA for contraception for <1, 1–2 and >5 years, in addition to 20 age-matched healthy women (nonusers), participated in this study. Lumbar spine BMD (LS-BMD) was measured by dual-energy X-ray absorptionmetry. Serum osteocalcin (OC), a bone formation marker, was measured by enzyme amplification sorbent immunoassay. Urinary deoxypyridinoline (DPD), a bone resorption marker, was determined by enzyme immunoassay.

Results

Serum OC and urinary DPD levels in women who used DMPA for <1, 1–2 and >5 years were significantly increased compared to the corresponding levels in nonusers. The increase of both biomarkers was more pronounced with longer duration of use. LS-BMD was significantly decreased in women on long-term DMPA use compared to LS-BMD in nonusers. The mean percentage decrease of LS-BMD in women who used DMPA for 1–2 and >5 years was 9% and 11.8%, respectively. LS-BMD was negatively correlated with serum OC and urinary DPD in women who used DMPA. On the other hand, LS-BMD and bone turnover were not significantly different between women who used DMPA for <1 year and nonusers.

Conclusion

Long-term use of DMPA (>2 years) had a significant adverse effect on BMD and induced increased bone turnover, as evidenced by a significant increase in biochemical indices of bone formation and resorption. The measurement of LS-BMD and of biomarkers of bone turnover may be recommended in women aged above 40 years and who used DMPA for a long duration (2–5 years).

Introduction

Depot medroxyprogesterone acetate (DMPA) has been widely used as a long-term reversible method of contraception for the past 30 years. It acts by inhibiting the secretion of pituitary gonadotropins, causing anovulation and alteration of the endometrium, which becomes atrophic with prolonged DMPA use. Both actions contribute to amenorrhea. Paiva et al. [1] and Gbolade et al. [2] reported that amenorrhea occurs in 45% of women who used DMPA. This proportion is increased when DMPA use is prolonged beyond 1 year.

Most women who use DMPA have hypoestrogenism [3]. Estrogen deficiency is consistently associated with bone loss, especially in young women [4]. However, recent data indicated that users of DMPA may have plasma estradiol (E2) levels close to menopausal values. Clark et al. [5] found that the median value of E2 was 57 pmol/L (15.4 pg/mL) during the 12 weeks of a DMPA cycle.

Cundy et al. [6] reported that bone density in women who use DMPA was intermediate between normal premenopausal women and postmenopausal controls. However, the effect of estrogen deficiency among long-term DMPA acceptors on bone mineral density (BMD) is still controversial, and additional knowledge on this field is necessary. Naessen et al. [7] and Petitti et al. [8] suggested that hormonal contraceptive use by young adult women is associated with small changes in BMD that occur early after initiation of use and are reversible. In contrast, Ott et al. [9] suggested that, in women who use DMPA, bone resorption exceeded bone formation.

Scholes et al. [10] reported that BMD levels among adolescents who use DMPA were lower than those of nonusers, and that discontinuers of DMPA experienced increased BMD relative to nonusers. Cundy et al. [11] demonstrated that women who use DMPA until menopause have attenuated rates of bone loss from the lumbar spine and the femoral neck postmenopause, presumably because they have already lost the estrogen-sensitive component of bones. Moreover, Berenson et al. [12] demonstrated that the loss of BMD associated with DMPA use appears to be linear during the first 2 years of use. However, Merkifeld et al. [13] observed no significant change in cortical bone mass among 23 DMPA users who were followed for 2 years.

Several biochemical markers that measure bone resorption and bone formation rates have been developed over the last decade, and they provide valuable information on bone physiology [9]. Osteocalcin (OC) and deoxypyridinoline (DPD) are reliable bone formation and bone resorption markers, respectively [14]. The aim of the present work was to identify any adverse effects on bone remodeling and bone density in long-term users of DMPA by the determination of the biomarkers of bone turnover and BMD.

Section snippets

Patients and methods

A retrospective cohort study was used to evaluate the effect of DMPA use on lumbar spine BMD (LS-BMD) and bone remodeling among women aged 21–44 years. The study enrolled 60 women; 40 women used DMPA and 20 participants (nonusers) did not use any hormonal method of contraception. All participants were recruited from the family planning and gynecology clinics of Al-Zahraa Teaching Hospital, Al-Azhar University Hospital and Cairo University Hospital. None had any history of smoking, alcohol

Results

DMPA users and nonusers were comparable with respect to mean age, parity, body mass index (BMI), previous history of contraception and previous history of lactation (Table 1). There were no significant differences between the two groups in terms of these clinical characteristics (p>.05). Table 2 shows the mean serum OC levels in DMPA users at different durations of use versus the levels in nonusers. The mean serum OC levels in women who used DMPA for <1, 1–2 and >5 years were significantly

Discussion

The present study demonstrates that there was no increase in bone resorption in women who used DMPA for <1 year, whereas women who used DMPA for >2 years had a significantly increased level of bone turnover markers and a significant decrease of LS-BMD when compared to the corresponding levels of age-matched healthy nonusers. These changes were more pronounced with advancing age and longer duration of DMPA use. Ott et at. [9] reported an increased rate of bone resorption in DMPA users, as

Conclusion

The present study revealed the following: (a) there were no significant changes in LS-BMD and bone remodeling among women who used DMPA for <1 year when compared to nonusers, indicating that short-term use of DMPA does not represent a heath hazard to skeletal mass; and (b) the long-term use of DMPA (>2 years) revealed a significant increase in bone turnover and a significant decrease of LS-BMD, indicating that long-term use of DMPA causes skeletal health disorder. In addition, the changes in

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