Adolescent Use of Combined Hormonal Contraception and Peak Bone Mineral Density Accrual

A Meta-analysis of International Prospective Controlled Studies

Azita Goshtasebi; Tatjana Subotic Brajic; Delia Scholes; Tamara Beres Lederer Goldberg; Abbey Berenson; Jerilynn C. Prior

Disclosures

Clin Endocrinol. 2019;90(4):517-524. 

In This Article

Abstract and Introduction

Abstract

Objective: Many women use combined hormonal contraceptives (CHC) during adolescence during which they are accruing peak areal bone mineral density (BMD) that relates to lifetime fracture risk. To build BMD requires formation with which CHC-related exogenous oestrogen may interfere. We compared peak BMD accrual in adolescents using and not using CHC.

Design/Participants: We performed literature searches for prospective published peer-reviewed articles providing 12- to 24-month BMD change in adolescent (12- to 19-year-old) women using CHC vs CHC-unexposed control women.

Methods: Meta-analyses used random-effects models to assess BMD change rate at lumbar spine (LS) and other sites in adolescent CHC users vs CHC nonusers.

Results: Literature searches yielded 84 publications of which nine were eligible. Adolescent-only data were sought from cohorts with wider age inclusions. The 12-month LS meta-analysis with eight paired comparisons in 1535 adolescents showed a weighted mean BMD difference of −0.02 (95% confidence interval [CI]: −0.05 to 0.00) g/cm2 in CHC-exposed adolescents (P = 0.04). The 24-month LS meta-analysis with five paired comparisons in 885 adolescents showed a highly significant weighted mean BMD difference of −0.02 (95% CI: −0.03 to −0.01) g/cm2 in CHC-exposed adolescents (P = 0.0006). Heterogeneities by I 2 were 96% and 85%, respectively. Insufficient data for other bone sites precluded quantitative analysis.

Conclusion: Given that adolescent exposure to CHC appears to be increasing, this evidence for potential impairment of peak spinal BMD accrual is of concern and suggests a potential public health problem. Randomized controlled trial data are needed to determine CHC effects on adolescent bone health.

Introduction

Combined hormonal contraceptives (CHC) are the most common birth control method used worldwide and are increasingly used by adolescent women.[1–3] CHC are proven effective for contraception and generally safe.[4] Because menopausal oestrogen treatment is positive for bone health, it has been assumed that CHC use would also be bone-protective. The association of CHC use with areal bone mineral density (BMD) change has only been documented since the mid-1990s.[5]

Adolescence is a key time in women's life cycle for bone accrual, for decreasing later life osteoporosis and lifetime fragility fracture risk.[6,7] Premenopausal BMD values are related to prevalent fractures in a cross-sectional evaluation of the adult population-based Canada-wide Canadian Multicentre Osteoporosis Study (CaMos).[8] Peak BMD at both the femoral neck and the total hip is gained in women between ages 16 and 19 years and lumbar spine peak BMD is achieved between ages 33 and 40 in prospective population-based data from the Youth and Adult CaMos Cohorts.[9] Those who achieve a lower peak BMD are widely believed to be at increased risk of later life fractures,[6,7] although prospective BMD and incident fragility fracture data are scarce.

Genetics accounts for more than 50% of peak bone mass; as well, a family history of fragility fracture has recently been shown to increase premenopausal BMD loss.[10] However, factors such as adequate calcium and other nutrition,[11] menstrual cycle/ovulatory disturbances[12] and physical activity[13] also influence peak BMD acquisition.

Increasingly, adolescent women are prescribed CHC for noncontraceptive indications such as cramps, acne and irregular cycles;[2] there is thus a need to understand the potential relationship of CHC use with adolescent women's peak BMD acquisition. CHC use may be a concern in adolescence because, to accrue peak BMD, active bone growth through modellingis necessary, and this requires bone formation. CHC has long been known to suppress bone remodelling.[14] Since oestrogen decreases bone turnover and suppresses bone resorption, it is positive for the adult skeleton that is generally in a state of bone loss. The dynamic bone state in adolescence is different. Supraphysiological ethinyl oestradiol (EE) doses are needed for effective contraception; therefore, use of CHC in adolescence may suppress bone growth as it suppresses bone resorption since the two processes are coupled.[2,3] Suppression of bone biomarker levels has been documented even with CHC EE doses as low as 20 μg which is considered "low dose" compared with earlier CHC products.[5,15,16]

We carried out a meta-analysis of published data reporting prospective BMD changes in healthy adolescent women with first use of CHC and in nonusing controls. Our hypothesis was that CHC use would impair adolescent BMD accrual.

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