Original research articleEstrogen–progestin contraceptive use during adolescence prevents bone mass acquisition: a 4-year follow-up study
Introduction
Osteoporosis is a skeletal disease affecting millions of people around the world. Genetic factors are thought to be the key determinants of bone mineral density (BMD) and bone mass, but environmental factors, such as physical activity, nutrition and, after puberty, sex steroid exposure, also influence the peak bone mass acquisition [1].
Estrogens and progesterone are known to have important effects on bone metabolism [2], [3]. Estrogens, in particular, have an important impact on bone physiology: they participate in sexual dimorphism of the skeleton and in maintaining the bone mineral homeostasis during reproduction and play an essential role in maintaining the bone balance in adults [4]. Estrogen therapy is known to be beneficial to postmenopausal bone [5], [6] and perimenopausal oral contraceptive (OC) use, even the low-dose formulations may prevent bone loss [7]. The skeletal effects of OCs in premenopausal women are not as evident. In general, it is believed that OCs are not harmful and might even be beneficial to the bone mass in premenopausal women [7], [8]. However, there have recently been increasing concerns that hormonal contraception during adolescent years alters the normal peak bone mass development [9], [10], [11].
Reduced circulating estrogen concentrations have been established to be the main cause for reduction in BMD in postmenopausal [12] and premenopausal [13] hypoestrogenic women. Estrogen-progestin contraceptives with low-dose formulations modify the circulating estrogen level by maintaining constant concentrations low, similar to those measured during early follicular phase [14]. This suppression of ovarian estrogen production might be the mechanism by which the estrogen-progestin and other hormonal contraceptive methods cause deficits in bone mass. These changes are, however, considered to be reversible after discontinuation of the therapy in young women [15].
Maximizing the peak bone mass may contribute to less frequent later life fractures. Puberty is a crucial time in bone development, and during that time, in girls, estrogen produces a large increase in bone mass and changes in bone geometry [16]. Gain in bone mass also continues in healthy young women during the third decade of life, but it ends at a point close to the age of 30 years [17]. The hormonal contraceptives change the normal hormone balance of an organism and, thus, may influence the normal bone mass accumulation.
Approximately half of the Finnish female adolescent university students use hormonal contraception [18]. Most hormonal contraception supplies the body with both estrogen and progesterone to suppress ovulation. At the present, the estrogen dose used in combined hormonal contraception is usually 35 mcg ethinyl estradiol (EE) or less. The estrogen amount has been reduced because of the risk of complications, such as thromboembolia.
In a cross-sectional study, low-dose estrogen OC use in young women has been found to be associated with lower BMD, as compared with their controls [19]. Young starting age [11], [20] and long duration of treatment [11] have been associated with lower BMD. Polatti et al. [10] found in a 5-year follow-up that long-term treatment with a monophasic pill containing 20 mcg EE and 150 mcg desogestrel prevented the physiologic occurrence of peak bone mass in 19–22-year-old adolescent women. The BMD of the control group increased 7.8% during the follow-up, while the BMD of the treatment group did not change [10]. Similar results have been established by others [20], [21].
On the other hand, no significant effect of estrogen–progestin contraception on bone was found in two 3-year follow-ups in older study populations [22], [23]. Some have found positive effects of oral contraceptive use on bone measurements in large population-based samples [24], [25].
Because hormonal contraception is in common use and the data of its skeletal effects continues to be contradictory, we performed the analysis of our follow-up study data. The aim of this analysis was to investigate whether EPC does influence bone mass acquisition in a population of Finnish adolescent women. We also studied to see whether the duration of therapy will have an association with the development of bone mass.
Section snippets
Participants
The study population was selected from the participants of a long-term health study with adolescent women since 1997. All participants who neither used hormonal contraception nor had a history of contraceptive use at the follow-up visit in 2000 were included in this study. The study population comprised 122 young women aged 12–19 years at inclusion. All participants were healthy and none had used any bone-affecting medication.
The participants were grouped after four follow-up years according to
Results
The baseline data of the three groups are shown in Table 1. There were no significant anthropometrical differences between the groups. The C2 group had higher MET value than the two other groups. The BMC of lumbar spine was higher in C2 group than in nonusers. Alcohol and tobacco use did not differ between groups during the entire follow-up.
Group C1 had used EPCs for 1.8 (S.D. 0.9) years. In group C2, the mean duration of contraceptive use was 3.5 years (S.D. 0.7).
The participants of this study
Discussion
The main finding of this prospective study of 4 years was that the increase of BMC in lumbar spine and femoral neck was smaller in the group of adolescent women who had used EPCs for more than 2 years. Most of the study population used low-dose estrogen (≤30 mcg) preparations.
The dose of EE could have an important effect in mediating the effect of hormonal contraception on bone health. Low-dose EPCs suppress the normal estrogen production by modifying the circulating estrogen levels to be as
Acknowledgments
Medical Research Foundation of the Turku University Central Hospital, The Finnish Medical Foundation and Turunmaan Duodecim Seura r.y. supported the study. Ansa Ojanlatva, Ph.D., is acknowledged for having made comments and suggestions to the manuscript.
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