Original research articleBone status after cessation of use of injectable progestin contraceptivesā
Introduction
Depot medroxyprogesterone acetate (DMPA), an injectable progestin contraceptive (IPC), has been in widespread use in many areas of the world since the 1960s and was approved for use in the United States in 1992 [1], [2], [3]. Another IPC, norethisterone enanthate (NET-EN), used in many developing countries, is not used in the United States [4]. There is biologic reason for concern about the bone health of IPC users. IPCs inhibit the secretion of pituitary gonadotropins, resulting in suppression of ovulation and the ovarian production of estrogen [5], [6], [7]. Both before and after menopause, lower levels of estrogen are associated with lower bone mineral density [8], [9], [10], [11], [12], which is associated with higher fracture risk [13], [14].
Cross-sectional and follow-up studies have found that women lose bone density while using IPCs and that bone density is recovered to some extent after cessation of use [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35]. It is still unclear whether the bone loss is completely reversible, how long recovery takes and whether recovery differs according to the age of the user. Most studies have focused on DMPA, and there is little information on the effect of NET-EN.
Since November of 2004, the US Food and Drug Administration has required a black box warning on DMPA labels, stating that users may lose significant bone mineral density, that bone loss may not be completely reversible and that DMPA should be used longer than 2 years only if other birth control methods are inadequate. The label also states that it is unknown if DMPA use during adolescence and early adulthood will reduce peak bone mass and result in increased risk of osteoporotic fracture in later life. The World Health Organization does not advise restrictions for the use of DMPA [36].
IPCs are commonly used in South Africa, often for long periods, by black women and women of mixed race [37]. We conducted a cross-sectional study in which we assessed the relation of calcaneus status measured by ultrasonography to IPC use among 3500 black women and women of mixed race in South Africa. This is the largest study by far to address lingering questions about the effects of IPC use on bone.
Section snippets
Materials and methods
The study was approved by institutional review boards of Boston University and the University of Cape Town.
Results
Table 2 gives adjusted mean values of BUA, SOS and QUI in categories of total years of IPC use and in categories of years since last IPC use from multivariable linear regression models. The two IPC variables were not adjusted for each other, i.e., they were assessed in separate regression models. For total years of IPC use, the mean values of BUA, SOS and QUI were lowest for women who had the longest durations of use (ā„10 years); the p values for trend for SOS and QUI to decrease as duration of
Discussion
Our results confirm previous findings that women who are using IPCs have lower bone measurements than women who have never used them [6], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32]. In addition, we found that the mean calcaneus measures of bone thickness among women who had stopped IPC use at least 2ā3 years previously were at least as great as those of never-users, regardless of duration of IPC use or age when it was used. These
Acknowledgments
The authors are grateful to Professor Vicky Lambert for advice, Eleanor Marks for her work on the study and to the nurses Beverly Arendse, Phoebe Gribble and Lungiswa Mankayi who conducted the interviews and ultrasound measurements.
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2009, ContraceptionCitation Excerpt :This association has led to concerns that BMD reductions induced by DMPA may lead to an increased long-term fracture risk; however, fragility fractures are very uncommon in premenopausal women and fracture risk is not significantly correlated with changes in BMD in women younger than 45 years [16]. Furthermore, as demonstrated in a recent systematic review of studies [17], we and others have shown that bone loss associated with DMPA use is substantially or completely reversed after DMPA use is discontinued [18ā24]. There is currently no evidence of a significant increase in the risk of fractures as a result of DMPA use [8].
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The present study was supported by grant HD042360 from the National Institute of Child Health and Human Development.