Transcript Polycystic Ovarian Syndromex

Sue Cote’ RNC WHNP
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The cycle begins with the first day of menstrual bleeding
A new ovum begins to mature in the ovaries
The sac around the maturing ovum produces estrogen,
increasing the levels in the body
Increasing estrogen levels prompt the uterine lining to thicken
Estrogen levels peak around day 14 and the sac, containing the
mature ovum, splits open releasing it from the ovary
The empty sac (corpus luteum) left in the ovary begins to
produce both estrogen and progesterone
Around day 22 the corpus luteum stops producing estrogen and
progesterone and if the egg has not been fertilized, both levels
will drop.
Blood vessels in the uterine walls contract and spasm due to the
lack of estrogen and progesterone and the uterine lining is shed
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Luteinizing hormone (LH) and follicle-stimulating
hormone (FSH) are called gonadotropins because
the stimulate the gonads-in males, the testes,
and in females, the ovaries
Theca cells in the ovary respond to LH
stimulation by secretion of testosterone, which is
converted into estrogen by adjacent granulosa
cells.
Ovulation of mature follicles on the ovary is
induced by a large burst of LH secretion.
FSH stimulates the maturation of ovarian follicles
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LH is present in low levels throughout the
woman’s cycle except for 1 ½ days prior to
ovuation.
Ovulation occurs about 10-12 hours after the
peak LH surge (this is what the ovulation kits
pick up), then returns to its low levels.
As a result of the ruptured follicle an increase
in the production of progesterone occurs to
help prepare the uterus for implantation.
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Most common endocrine disorder in women of
reproductive age
These women often have elevated androgen and LH
levels, an increased LH:FSH ratio, some increase in
serum estrogens, increases in fasting or challenged
insulin levels, decreased HDL levels with increased
triglycerides, and occasionally increased prolactin
levels.
Its etiology is not completely understood
Its treatment is based primarily on signs and
symptoms
Recent findings demonstrate that PCOS has
significant metabolic sequel including increased risk
for diabetes and CVD, (seven times increased risk of
heart attack and heart disease than other women)
 Irregular
menstrual cycles
 Infertility
 Signs
of androgen excess
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Can not rule out or make a diagnosis by the
appearance of the women
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Increased abdominal girth
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Increased dark hair
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Facial and back acne-cystic
 6.5%
or approximately 5
million women in the United
States.
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you add polycystic
ovaries as a criteria this
increases to 25 %
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Enlarged, smooth cystic ovaries were first
described in 1844-at that time it was
recommended to remove the ovary or do a
wedge resection.
1930’s-The notion that androgen production,
(which was always before felt to be the
province of the adrenal gland only), may be
associated with the ovary
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Menstrual cycle is fundamentally regulated by the
rhythmic release of the neuropeptide
gonadotropin-releasing hormone (GnRH)
Increased output of GnRH from the hypothalamus
is thought to be responsible for the hypersecretion of LH that acts on the theca cells to
augment ovarian androgen production
CNS stimulates the pituitary gland to secrete LH
which results in cyclical ovarian steroid output
Women with PCOS have an increased LH
Androgen production by the theca cells is LH
dependent
Defect associated with PCOS is unknown, however
women with this syndrome have several
interrelated characteristics
1. Insulin resistance
2. Evidence of androgen excess-for which there is
no other cause
3. Chronic oligo or anovulation (altered
gonadotropin dynamics)
4. An ultrasound appearance of polycystic ovaries
in the absence the above three characteristics is
NOT a basis for defining PCOS and should not
prompt a full evaluation
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Insulin is a hormone that has extensive
effects on metabolism and other body
functions, such as vascular compliance.
Insulin causes cells in the liver, muscle, and
fat tissue to take up glucose from the blood,
storing it as glycogen in the liver and muscle,
and stopping use of fat as an energy source.
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Abnormal insulin creates increased androgen,
but not the reverse. Weight loss will help correct
the symptoms of increased androgen, but
administration of gonadotropins does not result
in a reduction of insulin.
Insulin stimulates steroidogenesis, (the process
wherein desired forms of steroids are generated
by transformation of other steroids), in the
ovarian cells
Products of steroidogenesis include: androgens,
thestosterone, estrogens, progesterone,
corticoids, cortisol and aldosterone
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The condition in which normal amounts of insulin
are inadequate to produce a normal insulin
response from fat, muscle and liver cells.
The patients are not technically diabetic because
their glucose levels are normal.
Although obesity is associated with insulin
resistance, it can not be explained entirely by
obesity.
Difficult to diagnosis, fasting insulin levels may
be normal. Glucose tolerance testing where you
also measure the insulin levels may be more
accurate.
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Increased output of GnRH from the
hypothalamus is thought to be responsible
for the hypersecretion of LH that acts on the
theca cells to augment ovarian androgen
production
Reason unknown
Hyperinsulinism also increases the levels of
bioavailable androgen by reducing the
amount of sex hormone-binding globulin
(SHBG) produced by the liver
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Hirsutism – presence of terminal hair in a male like pattern.
Androgens directly transform vellus hair to terminal hair in
androgen sensitive areas. Male pattern distribution includes
hair growth on the face, chest, upper back, abdomen and
inner thighs.
Acne –sebaceous glands are strongly influenced by
androgens. The degree and severity of the acne is directly
associated with circulating androgen concentrations.
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Follicles in the ovaries of women with PCOS
do not mature fully-therefore estradiol
production by these follicules is limited.
Follicle Stimulating Hormone (FSH) is
absolutely essential for preovulatory follicle
growth-so impaired FSH signaling is a reason
for anovulation.
FSH secretion is constrained by negative
feedback inhibition
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Cycle duration greater than 35 days in
duration or less than eight cycles per year
Usually begins at menarche
Anovulation bleeding represents endometrial
breakthrough bleeding resulting from
continual estrogen stimulation unopposed by
progesterone.
Exclusion of other disordershyperprolactinemia, thyroid dysfunction,
androgen-secreting tumors, 21-hydroxylase
deficiency
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Dyslipidemia
Non-insulin-dependent diabetes mellitus
Gestational diabetes
Hypertension
Cardiovascular disease
Thrombosis
Endometrial cancer
Ovarian cancer
Breast cancer
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Baseline testosterone-greater than 40mg per
dL is significant
LH and FSH-greater than a 3:1 ratio
significant
Fasting Lipid Profile-triglycerides to HDLgreater than 5:1 significant
Insulin
DHEAS- levels vary with sex and age
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DHEA is a weak male hormone produced by
the adrenal gland. A naturally produced
prohormone.
Increase in DHEAS may be due to:
◦ Congenital adrenal hyperplasia (rare genetic
disorder)
◦ Non-cancerous tumor of the adrenal gland
◦ PCOS
Exercise
Weight
loss
Hair removal
Medications
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Oral contraceptives are used to both regulate
the menstrual cycle and suppress the
androgens.
Spironolactone affects the androgen
receptors and will, over a prolonged period of
time, reduce the hirsutism on its own.
Metformin has been shown to directly inhibit
androgen production in the human thecal
cells and to have a direct effect on ovarian
steroidogenesis. It also lowers insulin levels.
Management of Infertility
Diet and
exercise
Ovulation
No Ovulation
Clomiphene citrate use 50-150 mg
Consider metformin at this time
Ovulation
No ovulation
Use of clomiphene citrate with
referral
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Guzick David; Hoeger Kathleen Polycystic Ovary
Syndrome Clinical Updates in Women’s Health
Care Vol. VIII, Number 1, January 2009
Helfer Elizabeth A Practical Approach to Treating
Hirsutism Women’s Health Vol. 5 Number I
January-February 2005
Ruby Laura Polycystic Ovarian Syndrome The
Journal for Nurse Practitioners October 2008
697-704
Freeman Sarah Polycystic Ovary Syndrome:
Diagnosis and Management Women’s Health
Care Vol. 1, No.4 June 2002 15-20
Diet and
Exercise