Hypersecretion of adrenal androgens?

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PCOS : Symptoms &
Diagnosis
Pathogenesis (etiology?)
• Hypersecretion of adrenal androgens?
• Hypersecretion of ovarian androgens?
• A genetic disorder with an autosomal
dominant mode of inheritance?
• A multifactorial genetic disorder?
• Insulin resisrance 50%
decreased sensitivity to insulin in peripheral
tissues muscle and adipose tissue (but not in
hepatic tissue)
LH
FSH
acyclic
estrogen
Extra glandular
aromatization
Adipose tissue
Chronic
anovulation
follicular
maturation
Stim. Of stroma
and theca
Cyclic estrogen
Androgen
excess
Ovarian
androgen
Adrenal
androgen
Obesity
Insulin
SHBG
IGF-1
5-alfa reductase activity is
stimulated
Free
testosterone
IGF*** insulin like growth factor
Presentation
(STEIN-LEVENTHAL SYNDROM)
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Amenorrhea ,Oligomenorrhea
Infertility
Hirsutism
Acne
• OBESITY !
Other Symptoms
Courtesy of www.mja.com
• “Dirty Skin” or
Acanthosis Nigricans :
This condition causes
light brown to black rough
patches around the neck
and under arms.
• Migraines : Severe
headaches that cause
light sensitivity, nausea
and dizziness.
Androgen excess society 2006
All these factors :
• Hirsutism
and/or hyperandrogenemia
•Oligoanovolution and/or polycystic ovaries
• Exclusion of androgen excess or related
disorders
NIH consensus criteria
1990[1]
(all required)
Rotterdam criteria 2003*[2]
(two out of three required)
AES definition 2008[3]
(all required)
Menstrual irregularity due to
oligo- or anovulation
Oligo- or anovulation
Clinical and/or biochemical signs
of hyperandrogenism
Clinical and/or biochemical
signs of hyperandrogenism
Clinical and/or
biochemical signs of
hyperandrogenism
Ovarian dysfunction – oligoanovulation and/or polycystic
ovaries on ultrasound
Exclusion of other disorders:
NCCAH, androgen-secreting
tumors
Polycystic ovaries (by
ultrasound)
Exclusion of other androgen excess
or ovulatory disorders
Increased LH secretion: ??
•Ratio of LH/FSH 2-3
measurement of antimüllerian hormone
(AMH) concentrations may be useful in
the diagnosis/confirmation of PCOS,
although data are inconclusive and its
routine measurement is not currently
recommended
Increased androgen levels in blood
(testosterone , androstendione)
Increased LH, exaggerated surge
Increased fasting insulin
Increased estradiol and estrone levels
Decreased SHBG levels
Slightly rise in DEHEA
Increased prolactin
serum testosterone undergoes episodic
changes. Partly it is because norms are
standardized for early morning on days 4
through 10 of the menstrual cycle in
regularly cycling women because normal
testosterone levels fall 10 percent from
8:00 AM to 4:00 PM and rise transiently
during midcycle
Imaging
• ultrasonographgy
number of cysts in ≥12 cysts with
diameter of 2-9mm.
Long term risks in PCOS
• Type 2 diabetes
• Dyslipidemia
diminished HDL and increased LDL
• Endometrial cancer
Long term risks in PCOS
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Hypertension
Cardiovascular disease
Gestational diabetes mellitus
Ovarian cancer
Treatment
Oral Contraceptives
contain two major hormones for
ovulation : estrogen and
progestin.
oral contraceptive pills (OCPs) interfere with the
assessment of androgens. They suppress
gonadotropins, elevate SHBG, and directly inhibit
steroidogenic enzymes such as 3ß-hydroxysteroid
dehydrogenase (3ß-HSD). They normalize androgens
in PCOS
cuts the risk of endometrial cancer
50%.
If the woman is not hirsute and
does not desire pregnancy:
periodic withdrawal menses ,with
medroxyprogesterone acetate 10
days per month
decreasing peripheral estrogen
formation
(by weight reduction)
If pregnancy is desired
ovulation must be induced.
Insulin-sensitizing drugs, such as metformin
and the thiazolidinediones.
Clomiphene , letrozole
hMG, urofollitropin ,gonadorelin
• Laparoscopic electrocautery
persistence of ovulation and
normalization of serum androgens
and SHBG over many years
effect on insulin resistance and serum lipids
is not assessed
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