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Why We Shouldn’t Prescribe Hormonal Contraception to 12 Year Olds

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.

From Vihko and Apter (1984)

From Vihko and Apter (1984). These are from old site so you can click to embiggen.

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.

From Lipson and Ellison (1992)

From Lipson and Ellison (1992). These are from old site so you can click to embiggen.

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.

Painted rock that reads "Ellen congrats on beating teen pregnancy! Happy 20th birthday LSC 2010"

Birthday gift for a Northwestern student. Image by vxla on Flickr, Creative Commons license.

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//0022-3514.65.6.1243

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

Your Ability to Handle Your Environment is Correlated with your Hormones

Natural selection acts not on a behavior itself, but on the factors that produce that behavior, and/or the outcome of that behavior. So if we want to have an evolutionary explanation for a behavior, it’s important to understand both what drives it and its consequences. We also need evidence that this behavior (or again, what comes before or after it) has some clear fitness benefit.

The kinds of factors that produce variation in behavior include things like resource availability, group composition, and mating strategies. How much food does the individual have access to, but also what kind? What do they need to do to acquire it and do they need to compete to do so? Who else is in the group and are they related to her? Is she a seasonal breeder or spontaneous ovulator, a promiscuous, monogamous, or polygynous primate?

So there are certainly good reasons to expect many behaviors to have adaptive significance, and for them to improve reproductive success. Yet when it comes to studying humans, too often this evolutionary buttressing collapses, only to be replaced with pop evolution interpretations. These interpretations tend to forget that things we find sexy today may or may not have been preferred in ancestral environments, and that if we cannot understand relationships between behavior and reproductive success without some sort of mechanism, it is little more than storytelling.

Hormones are one surefire way to begin to build a mechanistic link between behavior and reproductive success. Yet I am usually rather ornery about those manuscripts as well. When I complain about articles about hormones and behavior, they usually are based on the following issues:

  • Use of a WEIRD population (Western, Educated, Industrialized, Rich, Democratic)
  • Infrequent sampling through the menstrual cycle, with no effort to determine ovulation
  • No clear mechanism to link the hormone and behavior
  • Evolutionary storytelling that doesn’t link to fitness benefits

So it’s nice to come across a paper* on hormones and behavior that not only manages not to fall into any of the above traps, but surpasses my expectations in terms of the quality of hypothesis testing, statistical analyses, and conclusions.

What they found
Ziomkiewicz et al (2012) found that urban, Polish women with a particular temperament profile – those with high activity and endurance traits but low emotional reactivity – had higher estradiol concentrations and a progesterone profile that rose earlier in the luteal phase compared to women with the opposite profile (low activity and endurance, high reactivity). They used the Formal Characteristics of Behavior – Temperament Inventory developed by Strelau and Zawadzki, and focused on activity, endurance and emotional reactivity because they correlate with personalities that indicate high reproductive success. In their supplementary materials, Ziomkiewicz et al more clearly define these traits:

“Emotional reactivity is the tendency to react intensively in response to emotional stimuli and is expressed by high emotional sensitivity and low emotional endurance. Endurance is the ability to react adequately in situations which require long-lasting or highly stimulative activity or under intensive external stimulation. Activity enables to maintain behaviors with high stimulative value or behaviors that provide high external stimulation” (Ziomkiewicz et al., 2012).

Therefore women with high activity and endurance, but low emotional reactivity – and thus are emotionally stable and extraverted – are called High Ability to Process Stimulation (HAPS) individuals. Those with low activity and endurance but high emotional reactivity – so neurotic and introverted – are called Low Ability to Process Stimulation (LAPS) individuals.

The participants of this study were healthy, urban women from Wrocław, Poland, and they collected urine daily for one menstrual cycle. While there were 116 total participants, the main analyses of the paper compare HAPS and LAPS women, of which there were 26 participants each. This is still a great sample size for a study that has so much analytical richness per participant – for comparison, my own dissertation has half the number of participants (n = 25), and my only other major dataset 46 participants.

Behavior is context-dependent
Ziomkiewicz et al took a life history perspective on the question of whether ovarian hormones play a role in women’s personality. Women who are better at processing stimuli probably have more resources available to them, which makes them better equipped to handle the high resource demands of pregnancy, lactation and childcare. Women who are better at processing stimuli in their environment tend to be more extroverted and sociable, and extraversion and sociability are both highly preferred traits in potential mates, as well as correlated with reproductive success.

So, the authors hypothesized that HAPS women would have hormone profiles that indicate higher fertility compared to LAPS women. This is a far more thoughtful way to develop hypotheses about behavior and ovarian hormones because it comes from a basic principle of understanding that behavior is dependent on context and resource availability. That is, behavior is influenced by underlying genetic variation, and also environmental variation.

Ultimately, what Ziomkiewicz et al are arguing is that the mechanisms that underlie the relationship between extraversion and reproductive success reflect a relationship between these more basic temperamental traits of how well one handles one’s environment and ovarian hormones. So they are developing a model for how behavior is correlated with ovarian hormones in a way that is functionally, biologically significant. I think this is really cool!

Within a given population, if you have higher estradiol concentrations than the norm, you likely are able to allocate more energy both to ovulating a high-quality egg and getting your endometrium to grow nice and thick. If you also have high progesterone concentrations, it means you have a nice, big corpus luteum (that’s the yellow body left behind by the ovulated egg, again indicating it was probably high quality). Further, high progesterone indicates you can not only decidualize your endometrium, which means give it all the nooks and crannies and growth factors that make it a nice place to implant, but you can maintain the endometrium and a potential trophoblast until the placenta can make its own progesterone. This increases the chance for implantation and pregnancy but may also reduce the risk of early pregnancy loss.

The reason I make the point that all of this matters in terms of intrapopulation variation, is that different lifestyles and subsistence behaviors help produce populational norms for hormone concentrations. What is high for a rural Polish woman, for instance, is not the same as high for an urban Polish woman, and is probably not the same as high for an urban American woman. Not only that, but since these behaviors are context and resource-dependent, then the contexts and resources available to a given population, and how much they vary based on socioeconomic status and many other factors, are also important.

Physiology is context-dependent
This paper is cool for behavior people, but it’s also cool for reproductive physiology nerds like me. I mean, look at these graphs!

Ziomkiewicz et al 2012 Figure 1 showing HAPS women have higher estradiol and an earlier progesterone curve than LAPS women.

Profiles of urinary estrogen (a) and progesterone (b) during the menstrual cycle in HAPS (black circle) and LAPS (white square) women.

These are very likely biologically significant differences, at least in the estradiol curves. The authors did find that the day dependency of progesterone was different in the two groups, and you can see that while the overall values aren’t that different, that the HAPS women have higher values in the early part of the luteal phase. I would like to see these values aligned by ovulation so we can better see them up against the implantation window, which is 6-12 days after ovulation. Aligning there rather than menses might give us some better insight into whether this difference is biologically meaningful. If progesterone is higher in HAPS women in the early part of the window, that would definitely be interesting. And of course, it would be interesting to one day also run these analyses alongside other physiological variables like follicle waves or endometrial thickness.

Meeting the criteria for a good behavior paper
As I mentioned before, the following issues make me cranky:

  • Use of a WEIRD population
  • Infrequent sampling through the menstrual cycle, with no effort to determine ovulation
  • No clear mechanism to link the hormone and behavior
  • Evolutionary storytelling that doesn’t link to fitness benefits for the behavior

Ziomkiewicz et al sampled daily throughout the menstrual cycle, provided a clear and coherent mechanistic link between hormones and behavior, and provided an interesting life history perspective on why temperament and ovarian hormones would be linked. The only criterion they don’t quite meet is in the use of an urban, Polish population, yet I still think this is different enough from the American and UK populations that are more often sampled that they pass here as well. From having done fieldwork in Poland over three summers, the activity patterns and diet composition is still pretty different in urban areas there versus in the US.

One final issue that Ziomkiewicz et al handle well is in discussing limitations and alternative hypotheses. They mention that energy availability can impact temperament, and so the relationship they found between temperament and ovarian hormones might only be the association between energy availability and ovarian hormones that has already been found countless times. However, they controlled for body fat, which partially addresses energy availability and the authors have previously shown influences estradiol.

Ziomkiewicz et al 2008 Figure 1 demonstrating that women with very high and very low body fat have lower estradiol concentrations

From Ziomkiewicz et al 2008. Women with very low and high body fat have lower estradiol in this sample.

Jasienska and Ellison 1998 Figure 3 showing the impact of energy expenditure on progesterone

From Jasienska and Ellison 1998, demonstrating that higher energy expenditure is correlated with lower progesterone concentrations in this sample of rural, Polish women.

At the same time, differences in energy availability using other measures like energy expenditure and intake tend to affect progesterone and luteal activity first, as you can see in the figure above, yet that was definitely the lesser finding in this study. So I really think the authors have something here.

Of course I am biased (remember to see*), but I do think Ziomkiewicz and colleagues have put together a thoughtful and important contribution to our understanding of the ways in which behavior and hormones influence each other.

*Full disclosure: I know several of the authors on this paper and two (Ziomkiewicz and Jasienska) are collaborators. However I knew nothing of this project or manuscript until I saw the final, published form.

Jasienska G, Ellison PT. 1998. Physical work causes suppression of ovarian function in women. Proceedings of the Royal Society of London Series B 265(1408):1847-1851.

Ziomkiewicz A, Ellison PT, Lipson SF, Thune I, Jasienska G. 2008. Body fat, energy balance and estradiol levels: a study based on hormonal profiles from complete menstrual cycles. Hum Reprod 23(11):2555-2563.

Ziomkiewicz A, Wichary S, Bochenek D, Pawlowski B, Jasienska G. 2012. Temperament and ovarian reproductive hormones in women: Evidence from a study during the entire menstrual cycle. Hormones and Behavior 61(4):535-540.

American Association of Physical Anthropology Meetings this week: Portland, Oregon

Another year, another podium presentation. This year I want to redeem myself: last year I rocked my first presentation on hormonal contraception (woo hoo!), then was too exhausted to be remotely coherent for my second on diet composition and C-reactive protein (though to be fair, I was also chairing that session). This year I have just one presentation, which will allow me to concentrate on my talk, but also enjoy the meetings more.

A few highlights from the AAPAs this year include:

  • Building Babies get-together on Wednesday night (look for Julienne Rutherford and some obvious signage at the reception that evening)
  • A Physical Anthropology Women’s Mentoring Network Happy Hour Thursday at 5:15pm in the Alexander’s Room on the 23rd floor of the Hilton
  • A Biological Anthropology Developing Investigators Troop Happy Hour from 6-7pm on Friday, also in the Alexander’s Room on the 23rd floor of the Hilton.

So if you were involved with our book, are looking to give or receive some lady mentoring, and/or are a junior bio anthro colleague, there are chances for you to meet up with others.

Then there are, you know, the talks. The stuff you do between the schmoozing and the drinking. The Building Babies Lady Editors are all in the same, late Friday session (Session 24 in the Galleria North, 2-6pm). Guess who has the 5:45 talk?

This girl.

The relationship between strenuous physical activity and C-reactive protein is cycle-phase dependent: results from rural Poland

Energetic and inflammatory variables impact ovarian functioning, but their mechanistic links to each other and the ovaries remain unclear. We hypothesize that inflammatory biomarker C-reactive protein (CRP) is negatively correlated with strenuous physical activity in a population of rural Polish women. Because progesterone is suppressed by physical activity, yet progesterone administration can increase physical activity, we further hypothesized that their activity patterns would vary between the follicular and luteal phases, periods of low and high progesterone. Using standard epidemiological methods to collect daily records of minutes and exertion of physical activity over one menstrual cycle, we distinguished between light and strenuous activity, and activity variation through the cycle. Saliva was collected daily (progesterone), and urine seven times over the cycle (CRP).

Midluteal progesterone concentrations were inversely correlated with luteal CRP (p = 0.02), median CRP (p = 0.05), and were positively associated with strenuous activity in the luteal phase (p = 0.09). Median, luteal and follicular CRP were all negatively correlated with strenuous activity in the luteal phase (p = 0.03 for all three measures). And when women were grouped into those with high and low CRP concentrations, those with low CRP performed significantly more strenuous physical activity through the luteal phase. None of these associations were found with follicular phase physical activity. These results suggest physical activity influences systemic inflammation, which may additionally influence ovarian functioning. Therefore continued attention on systemic inflammation is crucial to determine mechanistic links between it and reproductive success in women.

Since writing this abstract my thinking on the topic has matured a bit (this is part of the problem with having an abstract deadline in September for a conference in April). We’ve also played around with the data a bit more, and have some more to report. I hope my presentation will get us thinking about subsistence versus recreational physical activity, as well as variation in strenuousness. I expect some of this will turn out to be pretty relevant to variation in reproductive function.

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