Tuesday, August 31, 2010

Adolescent Menstrual Variation and Oral Contraceptives

The guest post below is by LEE alums Theresa and Ashley (currently skilled lab technicians planning their next steps in life!), with minimal editing by me. They did some fantastic research in their senior year and put together this blog post to teach the world about menstrual cycling in young girls. It's worth a read, and please comment with your thoughts!

Adolescent Menstrual Variation and Oral Contraceptives
By: Theresa Emmerling, Ashley Higgins and Kathryn Clancy

ResearchBlogging.orgMany informational videos and documentaries have been produced to inform young women on the changes that they will experience during puberty and upon first menstruation, also called menarche. Unfortunately, these explanations are quite often generalizations that can lead to misrepresentations of what is normal. The information available to young women today stresses normative values for menstrual cycle length rather than the wide degree of variation characteristic of their cycles and may have an impact on adolescents’ future choices concerning oral contraceptives.

Figure 1 from Vihko and Apter 1984
Most women are taught that the menstrual cycle is twenty-eight days long, with ovulation occurring at day 14, and that only tiny deviations from this are healthy. Teens are taught to expect that every month after first menses they will experience menstruation for about 5 days; however, most adolescents do not experience the average menstrual cycle. Many adolescents experience longer menstrual cycles, with the luteal phase lasting anywhere between four to thirteen days (Apter, 1978), and anovulation, where an egg is not released from the ovary, is the primary characteristic of their cycles (Figure 1, Vihko and Apter 1984). The HPO axis is not an “on/off” switch that commences a string of twenty-eight day menstrual cycles at menarche. Rather, it takes time for the pituitary to respond to LH surges, which occurs only after multiple exposures to GnRH and estrogen (Apter et al, 1978; Apter, 1997). Therefore, it can take an adolescent up to five years to begin seeing something closer to the average twenty-eight day cycle (Figures 1 and 2, Vihko and Apter 1984).

Figure 2 from Vihko and Apter 1984
To be fair, the challenge is determining what the normal variation in an adolescent’s cycle is and what is due to pathology: environmental factors and pathologies may influence the menstrual cycle during development of the HPO axis. Numerous studies have tried to pathologize what we believe is normal variation in adolescent menstrual cycles, calling them “menstrual disturbances” or characterizing them as some level of amenorrhea (Morimatsu et al, 2009). As of yet, there is no conclusive evidence. Many studies find correlations between irregular menstrual cycles and pathology (Singer et al, 2009), but do not control for oral contraceptives (i.e., van Hoof et al, 2004), other environmental factors that may influence the HPO axis (Christo et al, 2008), or the study consists of adolescents with an already known pathology (El-Khayat, 2008). The American Academy of Pediatrics published a paper in 2006 stating that while the definition of amenorrhea is the absence of menses for six or more months, adolescents should be examined after only three months and "not reassured that it is 'normal' to have irregular periods in the first gynecological years" (p. 2247).

Given that it is more common, even normal, for adolescents to have very long menstrual cycles, we are concerned with what looks like stronger criteria for amenorrhea in exactly the population where it is expected (though the AAP paper discusses the low frequency of very long cycles, it also fails to mention the frequency of the pathology they worry is hidden in these long cycles). Further, more stringent criteria that misrepresents normal variation in this group of women serves only to frighten a population already concerned about normality and fitting in. For many, the teenage years are a time when standing out is to be avoided, and anything that makes one seem abnormal – an early or late age at menarche, long or short menstrual cycles – can be a stigma and cause stress. Educating young women on the reality, that this variation is what is normal, and that if anything the 28-day cycle is abnormal at this life stage, may prevent some of the considerable misunderstandings they have about their health. Understanding one's own body is an important step in making educated, healthy choices in the future. If most young women do not actually experience what they are taught is the average menstrual cycle, despite the fact that the reality is that wide variation in menstrual cycle length is the primary characteristic of post-menarcheal cycling, we are providing information that could lead them to feel abnormal and want to treat what is likely healthy variation.

A source of serious concern stems from what’s happening in the doctor’s office. Doctors, particularly in the United States, prescribe oral contraceptives at the slightest mention of deviation from the norm or evidence of a “menstrual disturbance.” In 79% of cases, health care providers will prescribe OCs at the patient’s request (Andrista et al, 2004). Less than 5% of doctors offer alternative forms of contraception to their patients in the US (Gerschultz, 2007), despite the fact that intrauterine devices, or IUDs, are more widely prescribed globally, and are both safe and effective. Future research questions should address whether doctors believe OCs are the best choice for women or that they the easiest method to prescribe; further, it is important to understand the decisions involved in prescribing these hormone treatments to adolescents. We have found evidence of doctors prescribing oral contraceptives to girls as young as twelve years of age (Cromer et al., 2008). Additionally, doctors prescribe OCs for adolescents who do not “live a lifestyle conducive to menstruation” (Sucato, 2002). We worry that ingesting cocktails of exogenous hormones have become a tool of convenience without regard to the possible trade-offs in their consumption. There is a large gap in the literature concerning adolescents and the long-term effects of OCs, yet doctors’ primary concern is that adolescents will accidentally skip a couple pills every pack (Omar et al, 2005).

Natural variation in adolescent hormone levels is a largely unexplored realm of science, with the same handful of decades-old articles cited repeatedly. Further research will yield not only a better understanding of this "time of change" but also less pathologizing of natural variation. However, until that research is published and generally accepted in the scientific and medical communities, the prescription of OCs for adolescents should weighted against the possible long-term impacts of priming an immature HPO axis with hormones.


American Academy of Pediatrics Committee on Adolescence, American College of Obstetricians and Gynecologists Committee on Adolescent Health Care, Diaz A, Laufer MR, & Breech LL (2006). Menstruation in girls and adolescents: using the menstrual cycle as a vital sign. Pediatrics, 118 (5), 2245-50 PMID: 17079600

Andrist LC, Arias RD, Nucatola D, Kaunitz AM, Musselman BL, Reiter S, Boulanger J, Dominguez L, & Emmert S (2004). Women's and providers' attitudes toward menstrual suppression with extended use of oral contraceptives. Contraception, 70 (5), 359-63 PMID: 15504373

Apter, D, Viinikka, L, Vihko, R. (1978). Hormonal pattern of adolescent menstrual cycles. J of Clin Endocrinol Metab 47: 944-954.

APTER, D. (1997). Development of the Hypothalamic-Pituitary-Ovarian Axis Annals of the New York Academy of Sciences, 816 (1 Adolescent Gy), 9-21 DOI: 10.1111/j.1749-6632.1997.tb52125.x

Christo, K., Cord, J., Mendes, N., Miller, K., Goldstein, M., Klibanski, A., & Misra, M. (2008). Acylated ghrelin and leptin in adolescent athletes with amenorrhea, eumenorrheic athletes and controls: a cross-sectional study Clinical Endocrinology, 69 (4), 628-633 DOI: 10.1111/j.1365-2265.2008.03237.x

Cromer BA, Bonny AE, Stager M, Lazebnik R, Rome E, Ziegler J, Camlin-Shingler K, & Secic M (2008). Bone mineral density in adolescent females using injectable or oral contraceptives: a 24-month prospective study. Fertility and sterility, 90 (6), 2060-7 PMID: 18222431

El-Khayat, H., Soliman, N., Tomoum, H., Omran, M., El-Wakad, A., & Shatla, R. (2008). Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy Epilepsia, 49 (9), 1619-1626 DOI: 10.1111/j.1528-1167.2008.01622.x

GERSCHULTZ, K., SUCATO, G., HENNON, T., MURRAY, P., & GOLD, M. (2007). Extended Cycling of Combined Hormonal Contraceptives in Adolescents: Physician Views and Prescribing Practices Journal of Adolescent Health, 40 (2), 151-157 DOI: 10.1016/j.jadohealth.2006.09.013

Morimatsu, Y., Matsubara, S., Watanabe, T., Hashimoto, Y., Matsui, T., Asada, K., & Suzuki, M. (2009). Future recovery of the normal menstrual cycle in adolescent patients with secondary amenorrhea Journal of Obstetrics and Gynaecology Research, 35 (3), 545-550 DOI: 10.1111/j.1447-0756.2009.01014.x

Omar H, Kives S, & Allen L (2005). Extended use of the oral contraceptive pill--is it an acceptable option for the adolescent? Journal of pediatric and adolescent gynecology, 18 (4), 285-8 PMID: 16171734

Singer, K., Rosenthal, A., & Kasa-Vubu, J. (2009). Elevated Testosterone and Hypergonadotropism in Active Adolescents of Normal Weight with Oligomenorrhea Journal of Pediatric and Adolescent Gynecology, 22 (5), 323-327 DOI: 10.1016/j.jpag.2008.12.010


  1. How difficult is it to differentiate between menstrual disparities that are pathological and those that are not?

    It seems that in some cases (e.g, PCOS) it would be relatively simple (perhaps overly so) to characterize "menstrual disturbances" as a symptom of the syndrome, whereas in some cases it would be very difficult to trace the cause of the variation (e.g, common exogenous hormone sources, genetics).

    As conveyed by the authors, it seems that the predominant opinion of the medical community is that the status quo is sufficient in terms of prescription of oral contraceptives; that is, as long as OCs superficially address the complaint of the patient, they are sufficient as treatment for an array of similar maladies (or as the case may be, non-maladies being portrayed as pathological irregularities).

    I am curious as to what sorts of procedures could be implemented such that this overzealous prescription of OCs could be prevented. Obviously, further education of medical professionals would be required, but how do we go about producing satisfactory documentation regarding the existence of a normal "menstrual continuum," if you will?

    Such documentation will be hard to come by as long as doctors continue to lump patients with "menstrual disturbances" into one category.

  2. I think you raise some great questions, James. My guess is that the easiest way to differentiate between a long menstrual cycle due to energetic constraint (or something else equally benign) versus pathology would be to measure hormone concentrations daily for a period of time, and to do a fairly exhaustive survey of the patient's life, from her age at menarche, eating and exercise habits, stress, etc. But that would probably require non-invasive methods of collection like saliva or urine (because going in for daily blood would be a pain), and that just hardly ever happens even though it's a validated method.

    I think you made a particularly important point when you said: "it seems that the predominant opinion of the medical community is that the status quo is sufficient in terms of prescription of oral contraceptives; that is, as long as OCs superficially address the complaint of the patient, they are sufficient as treatment for an array of similar maladies (or as the case may be, non-maladies being portrayed as pathological irregularities)." This has been reported to me by parents of adolescents I know, as well as my own college-aged students, for the last ten years.

    But I'll stop here and give Theresa and Ashley a chance to respond as well!

  3. Another problem lies within the knowledge that we have of these particular pathologies. As you mentioned James, because PCOS encompasses a wide array of symptoms, it is easy to diagnose a patient as having some form of PCOS. However, this diagnosis says nothing of the woman's actual problem. What is the cause of these symptoms? The ease of prescribing oral contraceptives to lessen symptoms has made it possible for doctors to not actually seek out their causation. So, part of the solution is that doctors need to be more aware of these pathologies. I believe another major problem in distinguishing a pathological versus non-pathological menstrual disturbance lies in the doctor-patient interaction. How much information does a doctor gather regarding diet, exercise, stress (both physical and emotional)? In my experience, none of these questions were asked. Height and weight. Then oral contraceptives. If the doctor found out that a patient worked out extensively, perhaps that doctor would have the presence of mind to connect the two. Obviously, a diagnosis cannot be made by simply finding out the patient exercises 8 hours a day, but at least that information might lead the doctor to ask whether the disturbance is pathological or due to lifestyle. I have the suspicion that doctors rarely deal with these questions, as they seem to be concerned with simply treating symptoms.

  4. I am curious as to what sorts of procedures could be implemented such that this overzealous prescription of OCs could be prevented. Obviously, further education of medical professionals would be required, but how do we go about producing satisfactory documentation regarding the existence of a normal "menstrual continuum,"