No single etiologic factor fully accounts for the spec-trum of abnormalities in the polycystic

ovary syn-drome. In response to stimulation by luteinizing Whereas luteinizing hormone

regulates theandrogenic synthesis of theca cells, follicle-stim-ulating hormone is responsible for
regulating thearomatase activity of granulosa cells, thereby de-termining how much estrogen is
synthesized fromandrogenic precursors. When the concentration ofluteinizing hormone increases
relative to that offollicle-stimulating hormone, the ovaries prefer-entially synthesize androgen.
The frequency of the stimulus of hypothalamicgonadotropin-releasing hormone (GnRH) deter-
mines, in part, the relative proportion of luteiniz-ing hormone and follicle-stimulating hormone
syn-thesized within the gonadotrope (Fig. 2). Increasedpulse frequency of hypothalamic GnRH
favors tran-scription of theb -subunit of luteinizing hormoneover theb-subunit of follicle-
stimulating hormone;conversely, decreased pulse frequency of GnRH fa-vors transcription of
theb -subunit of follicle-stim-ulating hormone, which decreases the ratio of lute-inizing hormone
to follicle-stimulating hormone.
testosterone, and thus increases the proportion oftestosterone that circulates in the
unbound, biolog-ically available, or free, state. Because women withthe polycystic ovary
syndrome typically have hyper-insulinemia, the concentration of free testosteroneis often
elevated when the total testosterone con-centration is at the upper range of normal or
onlymodestly elevated.
The polycystic ovary syndrome remains one of themost common hormonal disorders in
women,with a prevalence estimated between 5 and 10 per-cent.20-22 Variance in prevalence
among popula-tions may reflect the effect of ethnic origin, race, andother environmental factors
on the phenotype. 23,24
Several lines of evidence suggest that the poly-cystic ovary syndrome is heritable, 25-29 and
variousapproaches have been initiated to attempt to definea specific genetic cause. 30,31 In
rare instances, sin-gle-gene mutations can give rise to the phenotypeof the
syndrome. 32 Current understanding of thepathogenesis of the syndrome suggests,
however,that it is a complex multigenic disorder. Candidategenes that may regulate the
hypothalamicpitu-itaryovarian axis, as well as those responsible forinsulin resistance and its
sequelae, have been theprincipal focus of linkage and casecontrol studies.Microarray analyses
of target tissues in the polycys-tic ovary syndrome 31 have been used to identify nov-el
candidate genes involved in the condition, and anumber of them appear to contribute modestly
tothe phenotype (Table 2).

testosterone, and thus increases the proportion oftestosterone that circulates in the unbound,
biolog-ically available, or free, state. Because women withthe polycystic ovary syndrome typically
have hyper-insulinemia, the concentration of free testosteroneis often elevated when the total
testosterone con-centration is at the upper range of normal or onlymodestly elevated.
The polycystic ovary syndrome remains one of themost common hormonal disorders in
women,with a prevalence estimated between 5 and 10 per-cent.20-22 Variance in prevalence
among popula-tions may reflect the effect of ethnic origin, race, andother environmental factors
on the phenotype. 23,24
Several lines of evidence suggest that the poly-cystic ovary syndrome is heritable, 25-29 and
variousapproaches have been initiated to attempt to definea specific genetic cause. 30,31 In
rare instances, sin-gle-gene mutations can give rise to the phenotypeof the
syndrome. 32 Current understanding of thepathogenesis of the syndrome suggests,
however,that it is a complex multigenic disorder. Candidategenes that may regulate the
hypothalamicpitu-itaryovarian axis, as well as those responsible forinsulin resistance and its
sequelae, have been theprincipal focus of linkage and casecontrol studies.Microarray analyses
of target tissues in the polycys-tic ovary syndrome 31 have been used to identify nov-el
candidate genes involved in the condition, and anumber of them appear to contribute modestly
tothe phenotype (Table 2). 30,57,58
The consequences of the polycystic ovary syndromeextend beyond the reproductive axis;
women withthe disorder are at substantial risk for the develop-ment of metabolic and
cardiovascular abnormali-ties similar to those that make up the metabolic syn-drome. 59 This
finding is not surprising, since boththe polycystic ovary syndrome and the metabolicsyndrome
share insulin resistance as a centralpathogenetic feature (Fig. 2). The polycystic ovarysyndrome
might thus be viewed as a sex-specificform of the metabolic syndrome, 60 and the
termsyndrome XX has been suggested as an apt termto underscore this association. 6