PCOS Twin Study - Environmental Factors in the Development of Polycystic Ovary Syndrome, Phase 2
Polycystic Ovary Syndrome, or PCOS, is the most common endocrine disorder in women.
Depending on the strictness of the diagnostic criteria used, it is thought to occur in about
6-10% of all women, many of whom do not know they have the syndrome. Women with PCOS
produce abnormally high levels of male hormones (hyperandrogenism); this counteracts their
ovaries' ability to make enough of the female hormones estrogen and progesterone needed for
normal menstruation. PCOS is the number one cause of hormonally related infertility and
also increases women's risks for diabetes, high blood pressure, hypercholesteremia,
cardiovascular disease and certain cancers. It is currently unclear to what extent PCOS and
PCOS-associated traits (hyperandrogenism, hyperinsulinemia, insulin resistance, type 2
diabetes, dyslipidemia, hypertension, obesity, and coronary artery disease) are the results
of environmental factors or genetic predisposition. Therefore, the NIEHS Program in
Clinical Research is conducting a multi-phase twin study to measure the extent of PCOS
heritability and to identify environmental and genetic factors involved in the development
of PCOS. The proposal described here is for Phase 2 of this study. The goals of Phase 2
are to: 1) establish more reliable concordance rates and baseline heritability estimates for
PCOS in MZ and DZ twins; and 2) establish a cohort of intact MZ and DZ female twin pairs
with PCOS as a resource for future studies.
In Phase 1, about 1500 individual female twins were identified from the Mid-Atlantic Twin
Registry (MATR) based on self report of a history of irregular periods and/or cystic ovaries
in the MATR General Health Screening Questionnaire. Those twins were surveyed by phone for
other traits associated with PCOS. In Phase 2, the twins most likely to have PCOS based on
their answers to the Phase 1 phone survey will be recontacted for further PCOS screening.
One or both twins in a pair will be screened for elevated levels of testosterone (total and
free testosterone, bioavailable testosterone or BaT; free androgen index or FAI).
Hyperandrogenism is one of the hallmark traits of PCOS and can be exhibited either
biochemically (elevated testosterone) or clinically (hirsutism, acne, hair loss, alopecia,
other). If one twin in a pair has an elevated BaT level, then both twins in the pair will
be asked to undergo a medical evaluation for PCOS confirmation. This includes a physical
exam, medical history, ultrasound, 2-hour glucose tolerance and other biochemical blood
tests, and a Ferriman-Gallwey evaluation for abnormal hirsutism (another characteristic of
PCOS). The women will also be tested for pregnancy and zygosity. Their female co-twins
will be invited to undergo a similar medical evaluation.
Depending on their PCOS traits, twin pairs in which neither member has elevated testosterone
levels might be asked to undergo the medical evaluation as well. In clinical practice, PCOS
diagnoses are often made on women with normal testosterone levels if they have other certain
PCOS traits. The determination to include pairs in which both members have normal
testosterone levels will be made depending on their collective PCOS traits that they
reported on their Phase 1 survey.
United States: Federal Government
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