– the hypothalamic-pituitary-ovarian axis is responding normally to abnormal conditions
normal physiology involves fluctuating estrogen levels; polycystic ovarian syndrome produces steady level of estrogen, which causes the hypothalamic-pituitary axis to produce
Ý LH and ß FSH
Ý
LH overstimulates the theca cells to produce androgen Þ hyperandrogenism (Þ hisuitism, virilization)
ß
FSH understimulates the granulosa cells to convert androgen to estrogen Þ inhibition of folliculogenesis (leads to many cysts on the ovary, polycystic ovarian syndrome)
steady estrogen levels lead to endometrial hyperplasia without differentiation (no progesterone), which in turn leads to irregular bleeding and could develop into atypical hyperplasia and cancer
Common Etiologies
– common factor is lack of the normal estradiol signal that initiates ovulation
obesity
– involves high peripheral conversion of androsteindione to estrone; low estrogen at end of menstrual cycle is masked by the high peripheral estrogen production
Þ hypothalamus does not signal start of new cycle
abnormal adrenarche
leading to disordered LH secretion
problems with hypothalamus
involving defective central GnRH pulse generation
intrinsic ovarian defect
such as insufficient granulosa cell aromatase
hyperinsulinemia
insulin mimics high LH, reduces sex hormone binding protein (Ý free androgen), ß IGF binding protein
other endocrine defects
such as primary hyperandrogenism, hypothyroidism, or hyperprolactinemia
Diagnosis
– generally through historyof irregular periods (irregular interval, amount and duration of flow)
laboratory diagnosis should be limited
and only used to rule out associated harmful conditions (i.e. hypothyroid, adrenal hyperplasia/tumors in virilized patients, insulin level screening is controversial)
Treatment
– cyclic progestin or oral contraceptives to prevent effects of unopposed estrogen (endometrial cancer, cardiovascular disease, diabetes)
these risks make it necessary to treat older women; treatment of younger women is controversial
an attempt to treat obesity should be employed at any age (most important)
treatment of symptoms
– should be tailored to the particular concerns of the patient; education is always important
for dysfunctional bleeding: cyclic progestin, oral contarceptives
if possible, cycling should be every two months to give the body a chance to ‘kick in’ on its own
for hiruitism: oral contraceptives, corticosteroids, aldactone, electrolysis
for infertility: ovulation induction (clomiphene: block pituitary estrogen receptors
Þ Ý FSH release)
(2) Hypoestrogenic Anovulation
–problem can be at the level of the hypothalamus or the ovary
(a) Hypothalamic Anovulation/Amenorrhea
– hypothalamus does not secrete enough GnRH Þ ß FSH and ß LH
normal state prior to puberty; abnormal if it occurs during reproductive years
Etiology
– anything that shuts down hypothalamic-pituitary axis: physical/mental stress, heavy exercise, pituitary tumors, weight loss, medications (tricyclics), Kallman’s syndrome (hypogonadotropic hypogonadism), Sheehan’s (post-partum infarction of the pituitary)
eating disorders are a very common etiology
Treatement Considerations
: osteoporosis, atherosclerotic heart disease
Treatment
– oral contraceptives or hormone replacement therapy
(b) Ovarian Failure
– ovaries do not respond to FSH, resulting in FSH levels (loss of negative feedback)
normal state after menopause; abnormal if it occurs during reproductive years ("premature menopause")
Etiology
– chromosomal abnormalities (Turner’s – should check in all women < 30); ovarian surgery, radiation, chemo