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Polycystic Ovary Syndrome
Polycystic Ovary Syndrome and the Impact of Obesity on Fertility
a report by
Anuja Dokras, MD, PhD
Associate Professor, Penn Fertility Care, University of Pennsylvania Medical Center, Philadelphia, PA
Polycystic ovary syndrome (PCOS) is the most common endocrine Pathophysiology of Polycystic Ovary Syndrome
disorder,
1
affecting 6–7% of women of reproductive age.
2
The syndrome Although PCOS is well recognized as a syndrome, its cause is not fully
is primarily characterized by irregular periods associated with determined. There is increasing evidence for a genetic basis,
11
and animal
anovulation, making it one of the main causes of infertility in women.
3
models suggest a role for fetal programming due to androgen excess.
12
PCOS also manifests with features of hyperandrogenism such as The syndrome may also be modified by environmental, dietary, and other
hirsutism, acne, and male-pattern hair loss. factors as its prevalence varies between populations.
11
Insulin resistance
and compensatory hyperinsulinemia have direct and indirect roles in the
Since its first description by Stein and Leventhal in 1935, PCOS has been pathogenesis of hyperandrogenism as exhibited in PCOS.
13
Elevated
predominantly thought of and treated as a gynecological complaint.
4
insulin levels, especially in women with central obesity, inhibit hepatic
Research over the past two decades has vastly improved our synthesis of sex-hormone-binding globulin (SHBG), thereby raising
understanding of PCOS, namely that in addition to reproductive circulating levels of free testosterone.
3
Higher levels of luteinizing
problems it also exhibits major metabolic and cardiovascular hormone act synergistically with insulin on ovarian theca cells to promote
morbidities.
5–8
production of androgens. Nevertheless, no abnormalities in insulin
receptor numbers or binding affinities have been detected within the
Diagnosing PCOS is complicated as the symptoms are heterogeneous and ovarian follicle. Constitutive increase in insulin receptor serine
vary with the age of the subject. There has been much debate on the phosphorylation has been reported.
13
precise criteria for diagnosing PCOS. At a National Institutes of Health
(NIH) conference in 1990, experts defined PCOS as the presence of Inter-related Factors in the Pathophysiology of
chronic oligo-ovulation/anovulation and biochemical/clinical hyper- Polycystic Ovary Syndrome
androgenism.
9
In 2003, a PCOS Consensus Workshop, convened in There is increasing evidence that obesity is strongly associated with
Rotterdam and sponsored by the European Society of Human PCOS. Overall, 30–50% of women with PCOS are obese; in some studies
Reproduction and Embryology (ESHRE) and the American Society for this figure is as high as 70%.
14
Typically, the obesity pattern is abdominal
Reproductive Medicine (ASRM), expanded the definition to include two or androidal and frequently precedes the onset of clinical manifestations
out of the three following criteria: oligo-ovulation or anovulation; clinical of PCOS.
7
Obese women with PCOS have a greater prevalence of
and/or biochemical signs of hyperandrogenism; and/or polycystic- menstrual disorders and hyperandrogenism (higher free testosterone and
appearing ovaries on ultrasound.
10
Ovaries are determined to be lower SHBG levels) than normal-weight PCOS women.
15,16
Furthermore,
polycystic if there are 12 or more follicles in each ovary measuring obese women with PCOS exhibit significant insulin resistance compared
2–9mm in diameter and/or increased ovarian volume. It was also with lean women with PCOS and obese controls.
17
Obesity modifies the
emphasized that the PCOS phenotype could be diagnosed only if other risk of type 2 diabetes and metabolic syndrome in women with PCOS,
5,7,18
medical conditions such as androgen-secreting tumors, congenital and there is also evidence of a link between obesity in the mother during
adrenal hyperplasia, Cushing’s syndrome, and hyperprolactinemia had gestation and the likelihood of the daughter developing hyper-
been ruled out.
2
androgenism and the PCOS phenotype later in life.
19
Intracellular visceral fat deposits induce insulin resistance in adipocytes
Anuja Dokras-Jagasia, MD, PhD, is an Associate Professor
at Penn Fertility Center, University of Pennsylvania Medical
and skeletal muscle; however, insulin synergistically stimulates androgen
Center, where she specializes in polycystic ovary syndrome, production in the theca cells of the ovaries.
13
As described earlier, insulin
pathophysiology of pre-eclampsia, and the role of tumor
decreases SHBG levels, thereby altering the ratio of free versus total
suppressor genes in the human placenta. Anuja received
her initial education in India, before taking a PhD in
testosterone in circulation. Insulin resistance is also linked to glucose
medicine at the University of Oxford in 1992. She completed intolerance, seen in a high percentage (20–49%) of obese women with
her post-graduate education at Yale University School of
PCOS but relatively uncommon in normal body mass index (BMI) women
Medicine, including time at New Haven Hospital. Anuja
moved to the University of Iowa in 1999, and to her
with PCOS.
13
Studies have shown that the increased prevalence of
current position in 2007. metabolic syndrome in obese women with PCOS correlates significantly
with insulin resistance.
7
In summary, insulin resistance/obesity modifies
the cardinal and metabolic features of PCOS.
© TOUCH BRIEFINGS 2007
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