Temple University Department of Anthropology

Menstrual Cycle Study

 

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SCIENTIFIC INFORMATION

 

Why is this an Anthropology study?

 

You’ve may have noticed that this study is being run through the Department of Anthropology at Temple University. Why Anthropology? Anthropology is the study of humans from a holistic perspective. Anthropology has 4 subfields, one of which is called Biological, or Physical, Anthropology. This subfield is concerned with humans as biological creatures. Biological Anthropologists study modern human biological variation and human evolution. Biological Anthropologists who study modern human biological variation (who sometimes call themselves “Human Biologists”) are, among other things, keenly interested in human reproduction. Why? You’d think that reproduction is something only physicians study. However, medical doctors are primarily interested in disorders and diseases – and how one goes from being healthy to developing a disease.

 

Unlike physicians, Human Biologists who study reproduction are interested in normal variation. That’s because our field rests firmly on the shoulders of Darwin’s theory of evolution by natural selection. Biological variation is a component of natural selection, and variation related to survival or reproduction is particularly important. So, expanding our knowledge about reproductive variation is critical to understanding the human evolutionary past.

 

Many Human Biologists who study reproduction are particularly interested in female reproduction. Why? If you think about it, human mothers’ investment in babies is huge: we’re pregnant for 9 months and then nurse our infants for several additional months. And that’s usually only for one baby at a time. Think of the amount of calories that women spend doing that! You have to ingest a lot of calories to successfully raise an infant if you’re human. From an evolutionary perspective, women’s reproduction is quite interesting.

 

 

What studies have been done on women’s reproduction in Human Biology?

 

For the most part, Human Biologists who study female reproduction have focused on how a woman’s lifestyle and life history impacts her reproductive health. You may be aware that women who are anorexic or who are elite athletes sometimes miss menstrual periods. By studying women’s hormone levels, Human Biologists have established that lifestyle factors, such as diet and exercise, can impact women’s reproduction in more subtle ways. To learn more about a recent study that investigated the impact a woman’s life experiences has on her reproductive health, click here (“Reproductive Fate Versus Environment”, Science, May 1, 2009, p. 589).

 

 

What roles might the uterus and genes play in variation in women’s reproduction?

 

Until recently, Human Biologists who were interested in women’s reproduction focused mostly on the ovaries, since you have to produce an egg – and you have to produce enough hormones to nurture that egg – in order to get pregnant in the first place. But what about the uterus? Isn’t it important in women’s reproduction? Although the uterus doesn’t produce hormones, it does respond to hormones that the ovaries produce. In fact, you can think of the hormones that the ovaries produce as “signals” to the uterus to prepare itself for pregnancy. What if women vary with regard to how their uteruses respond to these hormones, in addition to the amount of hormones that their ovaries produce? It turns out that both of the ovarian hormones, estrogen and progesterone, have receptors in the uterus. These receptors are what allow the uterus to respond to these signals from the ovaries. The estrogen and progesterone receptor molecules are proteins, and proteins are made according to instructions in our genes – our DNA. And just like variation in the genes that are responsible for hair, skin and eye color can make us look different, variants in the genes for hormone receptor proteins can alter how women’s uteri respond to the hormones their ovaries produce.

 

 

What gene are we investigating in this study?

 

As we designed our study, we looked for a genetic variant that might cause variation in how the uterus responds to ovarian hormones – and we found one! It’s called PROGINS, and it’s in the progesterone receptor gene. Research into the behavior of this variant at the molecular level indicates it that changes how cells respond to progesterone. PROGINS has also been studied as a risk factor for many women’s reproductive disorders, like cancers and endometriosis, but no conclusive links have been found. PROGINS is common among people of European descent (Caucasians), but rare among other groups. Because people of European descent are more likely to carry PROGINS, we are limiting our current study to Caucasian women. We have done some preliminary work on the worldwide distribution of PROGINS; scroll down to see more information about our publications.

 

 

What do we think this study will tell us?

 

Laboratory studies have shown that PROGINS changes how cells respond to progesterone. The cells that line the uterus are known to grow and change in response to progesterone and estrogen throughout the menstrual cycle. Given this evidence, we think that women who carry the PROGINS variant will have thicker uterine linings than women who do not. The thickness of the uterine lining can be measured by an ultrasound study of the uterus. Ultrasound is a technique that allows imaging of internal organs. An ultrasound wand or probe is placed near the organ of interest, and high-frequency sound waves allows the organ to be visualized on a screen. Unlike transabdominal ultrasound, in which an ultrasound wand is placed externally on the abdomen, transvaginal ultrasound involves a probe inserted into the vagina, which allows better visualization of the uterus than does transabdominal ultrasound. In addition to uterine thickness, our study participants also collect data about their menstrual cycles, to see if PROGINS affects menstruation.

 

We are also investigating whether a woman’s lifestyle impacts the thickness of her uterine lining or certain aspects of her menstrual cycle, regardless of whether she carries the PROGINS variant.

 

 

Why is this study important?

 

This study will greatly improve our knowledge about how genetic variation impacts the uterus. While the genetics behind uterine disorders such as endometrial cancer, fibroids, infertility, and endometriosis have been studied in some detail, no research has been done on how genes impact the normal, healthy uterus. As Human Biologists, we’re primarily interested in normal variation because it may impact reproductive fitness and evolution by natural selection. However, normal variation in the menstrual cycle and in the thickness of the lining of the uterus are related to risk for disorders such as infertility. So, expanding our knowledge in this area may clarify why some women are at higher risk for developing certain diseases.

 

 

Funding:

 

This study is funded by a Doctoral Dissertation Improvement Grant from the National Science Foundation and by a Dissertation Fieldwork Grant from the Wenner-Gren Foundation for Anthropological Research.

 

 

Findings:

 

The study is currently underway, and we’re still collecting data. Check back later for an update!

 

 

 

Publications:

 

¹ Rockwell LC, Arnson K, Rowe EJ, Jackson F, and Lorenz JG., Global distribution of human progesterone receptor genetic variants [Abstract program number 2607]. Presented at the annual meeting of The American Society for Human Genetics, November 12, 2008, Philadelphia, PA. Available after September 25, 2008 at the following URL: http://www.ashg.org/2008meeting/abstracts/fulltext/

 

Abstract: The progesterone receptor (PR) is a transcription factor that mediates the physiological actions of progesterone. Genetic variants of the PR gene have been investigated for associations with reproductive cancers (breast, ovarian, endometrial and prostrate) as well as other disorders and phenotypes (uterine fibroids, recurrent abortion, implantation failure following IVF, panic disorder, prolactin levels, and mammographic density) in several study populations self-identified as white/Caucasian. Little information exists about the frequency of potentially risk-conferring or protective variants in non-white populations. We genotyped 289 individuals from 21 populations derived from Europe, Asia, Africa, the Middle East, and North America, for 4 genetic variants of the PR (+331 G/A, PROGINS, rs561650, and rs608995). These populations include ethnic groups, geographically defined groups, and CEPH samples from Utah. Samples were obtained from Coriell Institute (Camden, NJ) or collected in the field with informed consent. +331 G/A, a single-base pair substitution in the promoter region which may increase transcription of the B isoform of the progesterone receptor protein, is polymorphic in all European populations but not elsewhere with the exception of one population in the Middle East (Druze) and one in Asia (Adygei). PROGINS, which includes an Alu insertion in intron G, occurs at highest frequency in the Middle East and European populations, lower frequency in the African-American population and CEPH samples, and is completely absent in the African and Asian populations excepting the Adygei. SNP rs561650 is polymorphic is all major geographic regions but absent in three populations: Senegal, Iberia and Cambodia. SNP rs608995 is polymorphic in all major geographic regions and all populations studied. The prevalence of progesterone-related reproductive cancers and disorders may differ among populations in part due to variable frequencies of these polymorphisms. (Support from Temple University.).

 

 

This information is approved by Temple University for public display and is associated with project 11489.