Shirin Kalyan PHD, Post-Doctoral Fellow  with CeMCOR

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Can women tell if they're cycling "egg-lessly"?

by Shirin Kalyan PHD, Post-Doctoral Fellow with CeMCOR

A new study, the "Menstruation and Ovulation Study", or MOS for short, is investigating whether women can tell if they ovulate or not. This is important because menstrual cycle and ovulation disturbances are common during both the beginning and the end of a woman's reproductive life. Both adolescent and perimenopausal women share problems with irregular periods, mood swings, cramps and heavy flow, in part because both have abnormal ovulation. A depiction of the cyclic nature of women's ovarian hormones through their life cycle is shown in Figure 1.

life cycles of ovarian hormones graph
Figure 1

An illustration of how estrogen and progesterone changes across women's life cycles. The chaotic surges of high estrogen and low progesterone levels are seen in both adolescence and perimenopause. [Figure adapted from Prior (2006) Perimenopause Lost. J Reprod Infant Psychol. 2006 Nov; 24(4):323-335.]

But what about women who have regular cycles and no problems? Could they be having a cycle but not releasing an egg (or ovulating)? Women between the ages of 20 and 40 are in the midst of their reproductive years and rarely have any reason to give their cycles a second thought. In fact, many doctors also work under the assumption that disturbed ovulation would be flagged by "funny periods" - such as having irregular bleeding patterns. However, there are a number of reproductive disturbances that often go undetected because they are silent within regular cycles. Anovulatory cycles are menstrual cycles in which either regular or irregular bleeding occurs without an egg being released. Luteal phase defects are another type of ovulation disturbance that often occur without notice. The time between when the egg is released (usually mid-cycle) and the time up until a woman's next period is referred to as the luteal phase (see Figure 2 below). During this time, progesterone levels significantly increase to prepare the endometrium for implantation of the egg should fertilization occur. This phase needs to be at least 12 days in length. If the time between egg release and the next period is less than 10 days, it is known as a short luteal phase. A short luteal phase results in reduced exposure to progesterone (in terms of both length of time and levels) and a failure to balance out the levels of estrogen in the body. Such ovulatory disturbances are more common during adolescence and perimenopause (Figure 1), but their prevalence in the midst of a woman's reproductive life cycle has yet to be fully investigated.

If you don't want to get pregnant, why does it matter whether or not you ovulate or have a normal luteal phase length? The reason why ovulation matters is because it is a reflection of the delicate balance between women's two important hormones: estrogen and progesterone. In any anovulatory cycle, these hormones are out of balance. Ovulation disturbances are the main cause for "estrogen dominance" which occurs when the levels of estrogen (the women's hormone level we know most about) are too high for the levels of progesterone (estrogen's essential, health-restoring partner hormone). This ying and yang relationship of estrogen and progesterone is essential because a hormonal imbalance is associated with important health issues for women. Cycles can have disturbed ovulation (meaning they are either anovulatory or have a short luteal phase) but don't show any menstrual cycle irregularities. Cycles that lack any overt sign that something is wrong are referred to as silent anovulatory cycles.

How many women at any given moment are having silent anovulatory cycles is hard to determine because there have been few studies that have actually investigated this. Because of this lack information, it is still unclear what characteristics or situations make women most susceptible to having chronically anovulatory menstrual cycles. Proper diagnosis is further impeded by the fact that a thorough investigation would require careful tracking of a woman's menstrual cycle with multiple hormone samples taken from blood, urine, or saliva throughout her cycle. One of the best indicators of true egg release is the rise in progesterone levels that occurs in the second half of the menstrual cycle, known as the luteal phase. The luteal phase is from egg release until the day before the next flow starts. Figure 2 shows the expected hormonal pattern that occurs during the normal menstrual cycle and the two main phases, the follicular and luteal, that define it.

Ovarian hormones graph
Figure 2

Because of the difficulty in assessing disturbed menstrual cycles, there have been only two studies so far that have looked at this issue in women randomly sampled from the population. These studies found that lack of ovulation (or anovulation) occurred about 10-18% of the time (1;2). Furthermore, in a one-year investigation that followed 66 healthy women who had to have two normal ovulatory cycles in a row to join the study, Dr. Jerilynn Prior's research group discovered that roughly 20% (or 13 out of the 66) had at least one anovulatory cycle during the year they were being monitored. However, despite the fact these cycles were anovulatory and didn't have any rise in progesterone during the luteal phase, there was no indication that anything was wrong, and the cycle appeared completely normal in regards to both flow and cycle length (3). Therefore, silent anovulation is most likely to be brought to medical attention when there have been problems with fertility.

Unfortunately, infertility isn't the only issue at stake. When ovulation doesn't occur, the unhealthy hormone imbalance that occurs when estrogen levels exceed progesterone levels is related to bone loss, heavy flow, and anemia in otherwise healthy young women (3-5). Lack of ovulation during women's younger years also has negative effects that may not appear until they are menopausal. These include increased risks for breast and endometrial (uterine lining) cancers (6) and possibly an increased risk of heart disease (7).

To address the gaps in our knowledge about what constitutes a normal ovulatory cycle and keeping with the goal to empower women, the Centre for Menstrual Cycle and Ovulation Research (CeMCOR) launched the Menstruation and Ovulation Study (MOS). MOS is a large study that is funded by the Canadian Institutes for Health Research (CIHR), and it aims to enroll 650 women between the ages of 20-40, who have all had a period at least once over the last 3 months, and who are not using hormonal contraception. The goal of MOS is to find out whether or not things women report about their cycles and health are related to their likelihood of ovulating in a particular cycle. This is currently a question that is difficult to an answer in both population studies as well as individual cases of fertility investigations. Why? Because a blood sample for progesterone needs to be carefully timed in the last week before the period, but not in the two days before flow. It would be a tremendous advantage if a a simple questionnaire could tell us that ovulation was occurring normally. This tool would allow assessments of ovulation in much larger studies of women than are now available.

If the findings from MOS validate the use of a questionnaire method to assess ovulation in women, it would be an invaluable tool in large randomly selected population studies in women's health research. In fact the very large Canadian Multicentre Osteoporosis Study (CaMOS, www.camos.org) of over 6,000 women randomly sampled around nine centres across Canada has asked these same questions. Thus the results of MOS will be immediately important for analysis of the CaMOS data and understanding the relationship between ovulation and bone density in Canada.

If we confirm that women appreciate changes in their experiences that indicate ovulation, we will also be able to use this knowledge to teach women to assess their own reproductive cycles and to be better able to interpret the subtle but important signals about ovulation that their bodies give them.


Reference List

  1. Swain MC, Bulbrook RD, Hayward JL 1974 Ovulatory failure in a normal population and in patients with breast cancer. J Obstet Gynaecol Br Commonw 81:640-643
  2. Sowers M, Randolph JF, Jr., Crutchfield M, Jannausch ML, Shapiro B, Zhang B, La Pietra M 1998 Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass. J Bone Miner Res 13:1191-1202
  3. Prior JC, Vigna YM, Schechter MT, Burgess AE 1990 Spinal bone loss and ovulatory disturbances. N Engl J Med 323:1221-1227
  4. Fraser IS 1990 Treatment of ovulatory and anovulatory dysfunctional uterine bleeding with oral progestogens. Aust N Z J Obstet Gynaecol 30:353-356
  5. Hallberg L, Hogdahl AM, Nilsson L, Rybo G 1966 Menstrual blood loss--a population study. Variation at different ages and attempts to define normality. Acta Obstet Gynecol Scand 45:320-351
  6. Coulam CB, Annegers JF, Kranz JS 1983 Chronic anovulation syndrome and associated neoplasia. Obstet Gynecol 61:403-407
  7. Mather KJ, Norman EG, Prior JC, Elliott TG 2000 Preserved forearm endothelial responses with acute exposure to progesterone: A randomized cross-over trial of 17-beta estradiol, progesterone, and 17-beta estradiol with progesterone in healthy menopausal women. J Clin Endocrinol Metab 85:4644-4649

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