Microsoft word - morin_papunen_laure

HYPERANDROGENISM IN FEMALE REPRODUCTION
Laure Morin-Papunen, Ph.D, M.D., University Hospital of Oulu, Finland
Androgens in women are synthesized for 25% in the ovaries, 25% in the adrenals and the
50% in the peripheral tissues. The most frequent causes of hyperandrogenism in women
are polycystic ovary syndrome (PCOS, 38-82%), congenital adrenal hyperplasia (CAH,
classical and non-classical, 1-3%) and androgen synthesizing tumors (ovarian and
adrenal, 0.6-2%).
Androgen secreting ovarian and adrenal tumors are extremely rare but should be
suspected in the presence of quickly worsening hirsutism and/or serum testosterone levels
higher than 6 nmol/l.
CAH is an inherited disorder of adrenal steroidogenesis, most usually caused by 21-
hydroxylase deficiency, resulting in decreased cortisol and frequently aldosterone
production, increased compensatory pituitary secretion of ACTH and, consequently,
excess adrenal androgen production. Compared with a non-CAH female population,
pregnancy and life-birth rates are severely reduced in salt-wasting patients, mildly
reduced in simple virilizing patients, and normal in non-classical patients. Several factors
have been suggested to contribute to the impaired fertility in CAH females: oligo-
anovulation due to adrenal androgen excess, persistent ovarian hyperandrogenism,
adrenal progesterone oversecretion, inadequate introitus and psychosexual factors such as
disturbed body image, delayed psychological development and reduced heterosexual
sexual activity in adulthood. Improving endocrine, surgical and psychological
management contribute to improving fertility chances in these patients.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder, affecting 5-10% of
women of reproductive age, (ASRM/ESHRE definition: two of the following criteria:
polycystic ovaries in ultrasonography, oligo-or amenorrhea, or evidence of
hyperandrogenism (clinical or biochemical). Women with PCOS exhibit a dysregulation
of GnRH pulse generator activities, with a disproportionately high LH secretion and
relatively constant low FSH secretion, and an elevated LH/FSH ratio. Chronic LH
stimulation induces hypersecretion of androgens and prevents the selection of the
dominant follicle. There is probably also a generalized dysregulation of ovarian androgen
secretion. Functional adrenal hyperandrogenism occurs in about 50% of women with
PCOS. Premature adrenarche seems to increase the risk of PCOS in adulthood. Insulin
resistance and hyperinsulinemia play a central role in the pathogenesis of PCOS.
Hyperinsulinemia results in increased ovarian androgen production and decreased sex
hormone binding globulin (SHBG) synthesis in the liver, leading to increased
bioavailability of free androgens. In vitro studies also indicate the existence of a
synergistic interaction between LH and insulin in promoting androgen secretion from
theca cells. This excess in local ovarian androgen production augmented by
hyperinsulinemia causes premature follicular atresia, anovulation, oligo-amenorrea and
anovulatory infertility. The hyperandrogenic milieu may also decrease the quality of the
riping ovum and disturb implantation of the embryo, but whether women with PCOS
have an increased miscarriage risk remains controversial. Several approaches have been
used for the treatment of infertility in women with PCOS. Weight reduction is the first line therapy for obese women. Ovulation induction is traditionally achieved with clomiphene citrate, gonadotropins or, less frequently, with laparoscopic ovarian drilling. The role of insulin-sensitizing drugs, such as metformin, remains controversial.

Source: http://endokrinologiyhdistys.yhdistysavain.fi/@Bin/174494/morin_papunen_laure.pdf