Aim There is an increased use of Hormonal Contraceptives (HCs) in female adolescents, during a period of growth, development and hormonal changes.1 2 Due to the limited long-term safety data available for adolescents, most of the guidelines that inform clinical practice for the use of HCs are extrapolated from adult safety data.3 This study aimed to provide a comprehensive review of the existing evidence on the safety profile of HCs use in adolescent girls under the age of 19 years.
Method A systematic review was carried out by searching through Medline, EMBASE, CINAHL, BNI and Cochrane Central Register of Controlled Trials for articles published between 2000-2019. All studies reporting side effects of HCs in young females, 19 years of age or under were included. The studies were not limited to those only using hormonal contraceptives for contraception purposes. In the main analysis we evaluated the association between the different hormonal contraceptives and the type of side effects. Two reviewers checked the quality of the studies and independently extracted data. Meta-analyses were performed, where possible, using random-effects model.
Results Fifty-two studies were included in the review, with an overall good quality picture. Of these, 28.8% (15/52) of them were included in the meta-analyses with a total of 6453 participants. The most reported side effect was changes in bone mineral density (BMD) (38%, 20/52), followed by changes in bleeding patterns (33%, 17/52) and weight gain (15%, 8/52). There was a significant association between the use of HCs and reduced bone development [spinal BMD mean difference -0.39, 95% CI -0.58 to -0.20, P<0.0001; femoral neck BMD mean difference -0.25, 95% CI -0.41 to -0.09, P=0.002; hip BMD mean difference -0.34, 95% CI -0.67 to 0.00, P=0.05] and altered bleeding patterns (OR 3.17; 95% CI 1.31 to 7.64; P=0.01) in female adolescents taking HCs.
Four studies (7.7%, 4/52) reported the association of using HCs with depression, mood changes and the initiation of the first use of antidepressant in young adolescents, with the highest odd ratio reported in teens aged 12–14 years (OR 3.46, 95%CI 3.04-3.94). Qualitative analysis further demonstrated the association of HCs use with the increased risk for early onset breast cancer in young females.
Conclusion This is the first comprehensive systematic and metanalysis review demonstrating the association of HCs use with significant adverse effects in adolescent girls. With the increasing adolescent exposure to HCs, further robust studies are warranted to determine the long-term safety profile specific to this population and inform current practice guidelines, especially with the rise in mental health illnesses in adolescents.4
Rashed AN, Hsia Y, Wilton L, et al. Trends and patterns of hormonal contraceptive prescribing for adolescents in primary care in the UK. Journal of Family Planning and Reproductive Health Care 2015;41:216–222.
De Leo V, Musacchio MC, Cappelli V, et al. Hormonal contraceptives: pharmacology tailored to women’s health. Human Reproduction Update 2016;22:634–646.
Faculty of Sexual and Reproductive Health Care. Contraceptive Choices for Young People (March 2010, amended May 2019). Available at: https://www.fsrh.org/standards-and-guidance/documents/cec-ceu-guidance-young-people-mar-2010/fsrh-guideline-contraception-young-people-may-2019.pdf (accessed 1 Dec 2020).
Ott MA, Shew ML, Ofner S, et al. The influence of hormonal contraception on mood and sexual interest among adolescents. Archive of Sexual Behaviour 2008;37:605–13. doi:10.1007/s10508-007-9302-0
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