This is a re-post, with slight editing, of a piece I wrote on the old blog after last year's AAPA meetings. I would like to keep thinking on this topic so thought I would share this before I write anything new for the Sci Am space.
Variation in adolescent menstrual cycles, doctor-patient relationships, and why we shouldn't prescribe hormonal contraceptives to twelve year olds
The United States has the highest rate of unintended teen pregnancy among industrialized nations. So I can understand why there are so many papers, and such a great effort, to get young girls on hormonal contraception (Clark et al. 2004; Clark 2001; Gerschultz et al. 2007; Gupta et al. 2008; Krishnamoorthy et al. 2008; Ott et al. 2002; Roye 1998; Roye and Seals 2001; Sayegh et al. 2006; Zibners et al. 1999).
But I’ve noticed two things: first, that hormonal contraception is used imperfectly in this population, with some estimates that 10-15% of adolescents on hormonal contraception still get pregnant (Gupta et al. 2008). Second, discontinuation rates for hormonal contraception in young girls are high, with many girls complaining about side effects, particularly breakthrough bleeding (Clark et al. 2004; Gupta et al. 2008; Zibners et al. 1999). I have to admit some concern over the fact that many of the papers I read that mentioned these discontinuation rates and side effects were almost condescending in their tone. The implication was that the side effects weren’t a big deal.
One of the ways clinicians and sexual health educators are trying to improve hormonal contraceptive use in adolescents is to emphasize their off-label use as a “regulator” – that is, the pill can regulate your cycle, regulate your mood, regulate your skin. The idea is to emphasize the positive effects of hormonal contraception to combat the side effects young girls both worry about, and actually experience. This also tends to produce campaigns and commercials with images of idealized young women that young girls would want to model themselves after – skinny, confident, and of course very feminine.
This is not my favorite idea. The pill should not regulate the cycles of adolescent girls who experience moderate variation in their cycles, which, as it turns out, is what characterizes the normal adolescent menstrual cycle. (This is independent from debilitating, pathological experiences of the menstrual cycle or menstrual bleeding, which occur in a very small percentage of women.)
Allow me to explain.
Vihko and Apter (1984) showed that there is variation in age at menarche, and that that variation tells us something about how long it should take an adolescent to start to achieve regular ovulatory cycles. The later your age at menarche, the longer you will experience irregular cycles. However, even in girls with ages at menarche twelve and under, it still took on average five years to achieve regular cycles. This indicates that, in adolescents, irregularity is in fact regular.
Lipson and Ellison (1992) have also looked at age-related variation in progesterone concentrations. Progesterone is the sex steroid hormone secreted by the ovary after ovulation, which is in the luteal phase. Luteal phase function is the one that seems to be the most variable within and between populations, and so progesterone is a great way to understand how female bodies vary. They found that those with the lowest hormone concentrations were on the extreme ends of their sample – 18-19 year olds, and 40-44 year olds and, as you might expect, hormone concentrations were higher as you moved towards the middle of that age range. So both younger and older women have low hormone concentrations relative to women in their reproductive prime, which is 25-35 years of age. But of course, this means that low hormone concentrations when you are in those early or late age ranges means that you are normal for your age.
Despite these issues, there are substantial benefits to hormonal contraception in adult women. When women take hormonal contraception in adulthood, particularly in the 25-35 year range, they are very effective contraception. The pill also may reduce risk of reproductive cancers, though results are mixed (Collaborative Group 1996; Collaborative Group 2008; Kahlenborn et al. 2006; Marchbanks et al. 2002; Modan et al. 2001; Narod et al. 1998; Smith et al. 2003). And of course, off-label use to treat painful periods or premenstrual syndrome can be beneficial for many (Fraser and Kovacs 2003).
However, the benefits of hormonal contraception in adults seems to be limited to more industrialized populations. Bentley (1994; 1996) first raised these concerns. She discussed the possible genetic, ethnic and developmental differences between women that could produce variation in pharmacokinetics, which could in turn vastly change the experience and efficacy of hormonal contraception in a global context. Virginia Vitzthum and others have also shown that there are high discontinuation rates and complaints of breakthrough bleeding in rural Bolivian women on hormonal contraception (Vitzthum and Ringheim 2005; Vitzthum et al. 2001). Other studies have shown similar discontinuation rates and side effects in other non-industrial populations (de Oliveira D'Antona et al. 2009; Gubhaju 2009).
You might notice that the issues in non-industrial populations mirror what has been seen in industrial adolescent girls. This isn’t surprising, given that they also have in common fewer ovulatory cycles and lower hormone concentrations.
So, I worry about whether the clear benefits of hormonal contraception in adulthood can be applied to adolescent girls, some as young as eleven or twelve years old. With the imperfect administration and high discontinuation rates, they aren’t that great as contraception. But there are additional, physiological concerns. What are the effects of giving doses of hormones to young girls with newly developing hypothalamic-pituitary-ovarian axes? The variation I mentioned before, where irregularity is regular in adolescence, is because the feedback loop between the brain and the gonads is priming and developing in this period, and this takes time. The sensitivity of the feedback loop is being set. If we flood this feedback loop with extra hormone, does this alter its sensitivity? It is a question worth testing.
Further, if we flood this immature system that normally has irregular cycles and low hormones, are we increasing lifetime estrogen exposure? High lifetime estrogen exposure is a risk factor for breast cancer and other reproductive cancers. Is it possible that hormonal contraception in adolescence could have the opposite effect of hormonal contraception in adulthood? Again, we need to test this hypothesis.
Future work on this topic includes asking whether adolescent menstrual cycle variation is any different today than twenty to thirty years ago. The only data we have (at least that I know of) are from the aforementioned 1984 and 1992 papers, and maybe some derivative papers using the same datasets. But we all know there have been massive changes in body composition, diet and health in the last few decades that deserve consideration. So, this work needs to be re-done on a current population.
We also need to ask how adolescent reproductive functioning varies within and between populations. While this has been studied extensively in adult women, we don’t have a sense of adolescent population variation. This will give us a sense of what ecological variables produce variation not only in age at menarche, but in how long cycle irregularity persists and reproductive hormone concentrations.
Some additional, provocative thoughts
In this symposium where I gave this talk, Karen Kramer delivered a beautiful paper just before mine on teen pregnancy, and I had some great conversations with session participants and attendees, that has further evolved my own thinking on this issue. I want to say something just a little provocative:
While I think teen pregnancy should be avoided, culturally we overstate its dangers and consequences because we have a real problem with young people reproducing. This can lead young girls to overlook potentially more serious issues like sexually transmitted infections, HIV, and cervical cancer, all of which girls and women are at risk for if they use only hormonal contraception and have otherwise unprotected sex.
Let me explain two important points here. First, in most industrialized nations we are not set up well to support young mothers because of the way families are isolated, yet social support is a strong predictor of birth weight, postpartum depression, and labor progression (Collins et al. 1993; Feldman et al. 2000; Turner et al. 1990). So there are very strong and obvious reasons why teen pregnancy and motherhood can be incredibly challenging in industrialized environments. I wonder sometimes if that lack of cultural support is related to a fear that more young girls will get pregnant if they feel they have permission to procreate. This is similar to the argument in favor of abstinence-only sex ed: if they don’t know their options, or are shamed into believing this option is the worst possible one, then of course they won’t make them. But adults aren’t rational. I’m unsure why we expect adolescents to be.
We also need to consider population variation in adolescence and pregnancy. Variation in age at first birth in traditional populations is quite wide, from sixteen to almost twenty six years of age (Walker et al. 2006). In more traditional populations you see a lot of allomothering and grandmothering to support first time mothers, who are often teenagers (Hawkes 2003; Hrdy 2009; Kramer 2005; Kramer 2008). So, support systems are built in, and it does not alter the trajectory of your life in the same way teen pregnancy does in an industrialized population.
This range of variation in age at first birth, and the fact that most of those young mothers do just fine, perhaps even end up with higher reproductive success, leads me to my second point: the physiological evidence against teen pregnancy might be overstated. In her talk, Karen discussed a paper of hers in the American Journal of Physical Anthropology that described the negative health outcomes of teen pregnancy (Kramer 2008). In it, she reviewed literature that suggests that when you control for lack of prenatal care, first pregnancy, and low socioeconomic status, the common assumption that pregnancy is harmful to teens is significantly weakened.
Further, in her own work with Pumé foragers in Venezuela, mothers under the age of fourteen were the only group to have greater infant mortality than the referent group of late reproducers (Kramer 2008). Yet when we teach young girls about their bodies, we tell them that their bodies are not equipped to have babies in their teens and that there are extreme consequences (in fact, I have said exactly this in the past). The reality is that those consequences are worst for very young teens, and may not be as significant in older teens.
Am I advocating teenagers get pregnant? Absolutely and unequivocally no. But I think they need access to correct information, not skewed information. This means telling them the truth about our uncertainties about the health implications for hormonal contraception in adolescence, it means educating them about the importance of barrier methods, and it means making sure they understand the health risks associated with unprotected sex.
This is a nuanced issue that requires nuanced thinking. Despite my concerns about adolescent hormone contraceptive use, there are problems with barrier methods as well, particularly when there may be a cultural bias against their use, or in situations when women cannot safely use contraception in an obvious way with their partner (Gupta et al. 2008). Again, what is important here is conveying correct information, so that each individual can weigh the pros and cons as they relate to her own context. This means it could be an excellent idea for some twelve year olds to be on hormonal contraception, and a terrible one for other girls through the age of twenty. It is going to have to be up to them.
I hope this post generates some thinking and some conversation, and I welcome people who might push me in a different direction than where I’m currently thinking. I am sharing this now, before putting it together as a manuscript, to provoke thoughts and comments.
References (watch out! Ref list almost as long as post!)
Bentley GR (1994). Ranging hormones: do hormonal contraceptives ignore human biological variation and evolution? Annals of the New York Academy of Sciences, 709, 201-3 PMID: 8154705
Bentley GR. 1996. Evidence for interpopulation variation in normal ovarian function and consequences for hormonal contraception. In: Rosetta LaM-T, C.G.N., editor. Variability in human fertility. Cambridge, UK: Cambridge University Press. p 46-65.
Clark, L. (2004). Menstrual irregularity from hormonal contraception triggers significant reproductive health fears in adolescent girls Journal of Adolescent Health, 34 (2), 123-124 DOI: 10.1016/j.jadohealth.2003.11.091
Clark, L. (2001). Will the Pill Make Me Sterile? Addressing Reproductive Health Concerns and Strategies to Improve Adherence to Hormonal Contraceptive Regimens in Adolescent Girls Journal of Pediatric and Adolescent Gynecology, 14 (4), 153-162 DOI: 10.1016/S1083-3188(01)00123-1
Collaborative group (1996). Breast cancer and hormonal contraceptives: collaborative reanalysis of individual data on 53 297 women with breast cancer and 100 239 women without breast cancer from 54 epidemiological studies The Lancet, 347 (9017), 1713-1727 DOI: 10.1016/S0140-6736(96)90806-5
Collaborative Group on Epidemiological Studies of Ovarian Cancer, Beral V, Doll R, Hermon C, Peto R, & Reeves G (2008). Ovarian cancer and oral contraceptives: collaborative reanalysis of data from 45 epidemiological studies including 23,257 women with ovarian cancer and 87,303 controls. Lancet, 371 (9609), 303-14 PMID: 18294997
Collins, N., Dunkel-Schetter, C., Lobel, M., & Scrimshaw, S. (1993). Social support in pregnancy: Psychosocial correlates of birth outcomes and postpartum depression. Journal of Personality and Social Psychology, 65 (6), 1243-1258 DOI: 10.1037//0022-35220.127.116.113
D'Antona Ade O, Chelekis JA, D'Antona MF, & Siqueira AD (2009). Contraceptive discontinuation and non-use in Santarém, Brazilian Amazon. Cadernos de saude publica / Ministerio da Saude, Fundacao Oswaldo Cruz, Escola Nacional de Saude Publica, 25 (9), 2021-32 PMID: 19750389
Feldman PJ, Dunkel-Schetter C, Sandman CA, & Wadhwa PD (2000). Maternal social support predicts birth weight and fetal growth in human pregnancy. Psychosomatic medicine, 62 (5), 715-25 PMID: 11020102
Fraser IS, & Kovacs GT (2003). The efficacy of non-contraceptive uses for hormonal contraceptives. The Medical journal of Australia, 178 (12), 621-3 PMID: 12797849
Gerschultz KL, Sucato GS, Hennon TR, Murray PJ, & Gold MA (2007). Extended cycling of combined hormonal contraceptives in adolescents: physician views and prescribing practices. The Journal of adolescent health : official publication of the Society for Adolescent Medicine, 40 (2), 151-7 PMID: 17259055
Gubhaju, B. (2009). Barriers to Sustained Use of Contraception in Nepal: Quality of Care, Socioeconomic Status, and Method-Related Factors Biodemography and Social Biology, 55 (1), 52-70 DOI: 10.1080/19485560903054671
Gupta, N., Corrado, S., & Goldstein, M. (2008). Hormonal Contraception for the Adolescent Pediatrics in Review, 29 (11), 386-397 DOI: 10.1542/pir.29-11-386
Hawkes, K. (2003). Grandmothers and the evolution of human longevity American Journal of Human Biology, 15 (3), 380-400 DOI: 10.1002/ajhb.10156
Hrdy SB. 2009. Mothers and others: the evolutionary origins of mutual understanding: Belknap Press.
Kahlenborn, C., Modugno, F., Potter, D., & Severs, W. (2006). Oral Contraceptive Use as a Risk Factor for Premenopausal Breast Cancer: A Meta-analysis Mayo Clinic Proceedings, 81 (10), 1290-1302 DOI: 10.4065/81.10.1290
Kramer, K. (2005). Children's Help and the Pace of Reproduction: Cooperative Breeding in Humans Evolutionary Anthropology: Issues, News, and Reviews, 14 (6), 224-237 DOI: 10.1002/evan.20082
Kramer KL (2008). Early sexual maturity among Pumé foragers of Venezuela: fitness implications of teen motherhood. American journal of physical anthropology, 136 (3), 338-50 PMID: 18386795
KRISHNAMOORTHY, N., SIMPSON, C., TOWNEND, J., HELMS, P., & MCLAY, J. (2008). Adolescent Females and Hormonal Contraception: A Retrospective Study in Primary Care Journal of Adolescent Health, 42 (1), 97-101 DOI: 10.1016/j.jadohealth.2007.06.016
Lipson, S., & Ellison, P. (2008). Normative study of age variation in salivary progesterone profiles Journal of Biosocial Science, 24 (02) DOI: 10.1017/S0021932000019751
Marchbanks, P., McDonald, J., Wilson, H., Folger, S., Mandel, M., Daling, J., Bernstein, L., Malone, K., Ursin, G., Strom, B., Norman, S., Wingo, P., Burkman, R., Berlin, J., Simon, M., Spirtas, R., & Weiss, L. (2002). Oral Contraceptives and the Risk of Breast Cancer New England Journal of Medicine, 346 (26), 2025-2032 DOI: 10.1056/NEJMoa013202
Modan B, Hartge P, Hirsh-Yechezkel G, Chetrit A, Lubin F, Beller U, Ben-Baruch G, Fishman A, Menczer J, Struewing JP, Tucker MA, Wacholder S, & National Israel Ovarian Cancer Study Group (2001). Parity, oral contraceptives, and the risk of ovarian cancer among carriers and noncarriers of a BRCA1 or BRCA2 mutation. The New England journal of medicine, 345 (4), 235-40 PMID: 11474660
Narod, S., Risch, H., Moslehi, R., Dørum, A., Neuhausen, S., Olsson, H., Provencher, D., Radice, P., Evans, G., Bishop, S., Brunet, J., Ponder, B., & Klijn, J. (1998). Oral Contraceptives and the Risk of Hereditary Ovarian Cancer New England Journal of Medicine, 339 (7), 424-428 DOI: 10.1056/NEJM199808133390702
Ott, M., Adler, N., Millstein, S., Tschann, J., & Ellen, J. (2002). The Trade-Off between Hormonal Contraceptives and Condoms among Adolescents Perspectives on Sexual and Reproductive Health, 34 (1) DOI: 10.2307/3030227
ROYE, C. (1998). Condom use by hispanic and african-american adolescent girls who use hormonal contraception Journal of Adolescent Health, 23 (4), 205-211 DOI: 10.1016/S1054-139X(97)00264-4
Roye CF, & Seals B (2001). A qualitative assessment of condom use decisions by female adolescents who use hormonal contraception. The Journal of the Association of Nurses in AIDS Care : JANAC, 12 (6), 78-87 PMID: 11723916
SAYEGH, M., FORTENBERRY, J., SHEW, M., & ORR, D. (2005). The developmental association of relationship quality, hormonal contraceptive choice and condom non-use among adolescent women Journal of Adolescent Health, 36 (2), 97-97 DOI: 10.1016/j.jadohealth.2004.11.009
SMITH, J., GREEN, J., DEGONZALEZ, A., APPLEBY, P., PETO, J., PLUMMER, M., FRANCESCHI, S., & BERAL, V. (2003). Cervical cancer and use of hormonal contraceptives: a systematic review The Lancet, 361 (9364), 1159-1167 DOI: 10.1016/S0140-6736(03)12949-2
Turner, R., Grindstaff, C., & Phillips, N. (1990). Social Support and Outcome in Teenage Pregnancy Journal of Health and Social Behavior, 31 (1) DOI: 10.2307/2137044
Vihko R, & Apter D (1984). Endocrine characteristics of adolescent menstrual cycles: impact of early menarche. Journal of steroid biochemistry, 20 (1), 231-6 PMID: 6231419
Vitzthum, V., & Ringheim, K. (2005). Hormonal Contraception and Physiology: A Research-based Theory of Discontinuation Due to Side Effects Studies in Family Planning, 36 (1), 13-32 DOI: 10.1111/j.1728-4465.2005.00038.x
Vitzthum, V. (2001). Vaginal bleeding patterns among rural highland Bolivian women: relationship to fecundity and fetal loss Contraception, 64 (5), 319-325 DOI: 10.1016/S0010-7824(01)00260-8
Walker, R., Gurven, M., Hill, K., Migliano, A., Chagnon, N., De Souza, R., Djurovic, G., Hames, R., Hurtado, A., Kaplan, H., Kramer, K., Oliver, W., Valeggia, C., & Yamauchi, T. (2006). Growth rates and life histories in twenty-two small-scale societies American Journal of Human Biology, 18 (3), 295-311 DOI: 10.1002/ajhb.20510
ZIBNERS, A., CROMER, B., & HAYES, J. (1999). Comparison of continuation rates for hormonal contraception among adolescents Journal of Pediatric and Adolescent Gynecology, 12 (2), 90-94 DOI: 10.1016/S1083-3188(00)86633-4