Mini Review - sepeap

358 Nader: Adrenarche And Polycystic Ovary Syndrome
animals, conception is timed to ensure that birth takes
place in a season when food and climatic conditions
are appropriate. 79 Women affected by the Dutch famine
of 1944e45 at ages 3e13 years had a 1.9-fold
higher risk of having fewer than the desired number
of children in their lifetime. 80
Unfortunately, in the western hemisphere, where
the food supply is plentiful, there is maladaptation.
This may be exacerbated by an adverse intrauterine
environment followed by excess catch-up growth, by
genetic insulin resistance, often compounded by obesity
or by a thrifty genotype. 78 Under such circumstances,
early and excessive production of androgens
from the adrenals promotes growth, development,
and bone maturation, and leads to excessive LHinduced
ovarian androgen production. These events
hasten gonadarche but hinder full gonadal maturation
and the establishment of ovulatory cycles. This state
of hyperandrogenism, anovulation, and cystic ovarian
morphology is what we call PCOS.
Challenges and Future Directions
We need to move away from the concept of a single
path to PCOS toward a broader view of its pathogenesis,
encompassing multiple derangements. What we
call PCOS is likely to be a diverse group of disorders
with similar clinical manifestations and shared biochemical
features. There will be commonalities and
differences in these different entities. Should they
all be called PCOS? For example, non-classic or
late-onset congenital adrenal hyperplasia is really
a form of PCOS, with clinical manifestations that are
virtually identical. The partial deficiency of the 21-
hydroxylase enzyme responsible for the commonest
form of this disorder does not manifest itself clinically
during early childhood. As the zona reticularis develops
and is stimulated, excessive amounts of adrenal
androgens are produced. 81 This androgen excess
not only leads to hirsutism, but hinders the establishment
of normal ovulatory cycles. We do not call it
PCOS because we understand its pathophysiology
and genetics and categorize it as a separate entity.
Thus it would seem that our task should begin by
cataloging androgen excess disorders, determining
their associations, biochemical pathways, and genetics.
Only by doing so can we rationally approach prevention
and treatment of this common reproductive
problem and its many consequences.
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