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Fadhila Al-Busaidi
family medicine R4
F 22 yrs old lady, unmarried,
c/o irregular period since 2 yrs.
Her period comes every 2-3 months.
normal flow , no inter-menstrual bleeding
She gained 20kg in the past 18 months.
O/E:
Obese lady, BMI 30
BP: 125/80 . HR: 75
Grade II acne over her face.
Mild fine hair growth , face .
Thyroid: normal.
Systemic examination normal.
Epidemiology and pathophysiology.
Clinical manifestation.
Diagnosis.
Management.
PCOS is the most common
endocrinopathy among reproductive-aged
women in the United States, affecting
approximately 7% of female patients.
Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the
polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-2749.
 Has been linked to altered (LH) action, insulin resistance,
and a possible predisposition to hyperandrogenism.
 One theory maintains that underlying insulin resistance
exacerbates hyperandrogenism by:
• suppressing synthesis of sex hormone–binding globulin and
• increasing adrenal and ovarian synthesis of androgens, thereby
• increasing androgen levels.
 These androgens then lead to irregular menses and
physical manifestations of hyperandrogenism
Hyperandrogenism
• Acne, androgenic
alopecia, hirsutism
• Testosterone,
dehydroepiandroster
one.
Ovulatory dysfunction
• Oligoamenorrhea
• amenorrhea
Polycystic ovary
• 12 or more follicles
( or 25 in new US
technology ).
• Each measuring 2-9
mm
• OR ovary volume
>10ml.
Rotterdam criteria:
Diagnosis requires the presence of at least
two of the following three findings:
 Hyperandrogenism,
Ovulatory dysfunction,
Polycystic ovaries.
]AAFP and RCOG[
 Diagnosis can generally be accomplished
with a careful history, physical
examination, and basic laboratory testing,
without the need for ultrasonography or
other imaging.
]AAFP[
 PCOS is associated with metabolic syndrome.
 About one-half of women with PCOS are obese.
 Increase risk of cardiovascular disease.
 Fourfold increase in the risk of T2DM.
 Increased prevalence of nonalcoholic fatty liver
disease, sleep apnea, and dyslipidemia in patients
with PCOS, even when BMI is controlled.
 Increased risk of mood disorders among patients
with PCOS
 the American College of Obstetricians and
Gynecologists recommend that clinicians
evaluate:
 blood pressure at every visit,
 lipid levels at the time of diagnosis,
 screen for T2DM with GTT regardless of a
patient’s BMI.
 Patients should have repeat diabetes
screening every 3-5years, or more often if
other indications for screening are present.
There is no need to order laboratory
testing for these conditions if the patient
does not have suggestive physical
findings.
Not necessary
A ratio >2 generally indicates PCOS, but
there are no exact cutoff values because
many different assays are used. The FSH
level is more helpful in ruling out ovarian
failure.
Anovulation is common after menarche, so
it is reasonable to delay workup for PCOS
in adolescents until they have been
oligomenorrheic for at least two years.
If an adolescent is evaluated for PCOS, it
has been suggested that she meet all
three of the Rotterdam criteria before
being diagnosed with the condition.
Treatment should be individualized based
on the patient’s presentation and desire for
pregnancy.
Lifestyle modification and weight reduction
reduce insulin resistance and can
significantly improve ovulation.
 Lifestyle modification considered as first-
line therapy for women who are
overweight. AAFP
clomiphene citrate (50–100 mg).
Successful in inducing ovulation in 75–
80% of women.
Needs Ultrasound monitoring to minimise
the 10% risk of multiple pregnancy, and to
ensure that ovulation is taking place
]NICE[
 The Endocrine Society recommends
clomiphene or letrozole (Femara) for
ovulation induction. AAFP
 Recent studies suggest that letrozole is
associated with higher live-birth rates and
ovulation rates compared with clomiphene in
patients with PCOS.
Legro RS, Brzyski RG, Diamond MP, et al.; NICHD Reproductive Medicine Network. Letrozole versus
clomiphene for infertility in the polycystic ovary syndrome [published correction appears in N Engl J
Med. 2014; 317(15):1465]. N Engl J Med. 2014;371(2):119-129.
 The impact of metformin on fertility is controversial;
although it was once believed to improve infertility,
a 2012 Cochrane review concluded that it does
not. AAFP
 Metformin alone may improve the rate of ovulation,
but results of a large RCT shows that metformin
will result in a live birth rate of only 7%. In the
same RCT, metformin added to clomiphene
conferred no additional benefit in terms of live birth
rate compared with clomiphene alone. NICE
 In a patient not seeking pregnancy, hormonal
contraception is the initial medication for
treatment of irregular menses and
hyperandrogenism manifesting as acne or
hirsutism.
 No superiority of one oral contraceptive over
another in treating PCOS.
 Prevention of endometrial hyperplasia from
chronic anovulation may be accomplished by
progesterone derivatives.
Small studies have shown that metformin
can restore regular menses in up to 50%
to 70% of women with PCOS, but oral
contraceptives have been shown to be
superior to metformin for regulating
menses and lowering androgen levels
Romualdi D, De Cicco S, Tagliaferri V, Proto C, Lanzone A, Guido M. The metabolic status modulates the effect of metformin on
the antimullerian hormone-androgens-insulin interplay in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab.
2011;96(5):E821-E824.
 According to a 2015 Cochrane review, the
most effective first-line therapy for mild
hirsutism is oral contraceptives.
 Spironolactone, 100 mg daily, and flutamide,
250 mg twice daily, are safe for patient use,
but the evidence for their effectiveness is
minimal.
 Electrolysis, or lasers and intense pulsed
light.
Hormonal contraceptives are first-line
medications for treating acne associated
with PCOS, in conjunction with standard
topical acne therapy (e.g., retinoids,
antibiotics, benzoyl peroxide) or as
monotherapy.
Antiandrogens, spironolactone can be
added as second-line medications.
 Serum testosterone >5 nmol/l (to exclude other
causes of androgen excess, e.g. tumours, late
onset congenital adrenal hyperplasia, Cushing's
syndrome)
 Infertility
 Rapid onset of hirsutism (to exclude androgen
secreting tumours)
 Glucose intolerance/diabetes
 Amenorrhoea of more than 6 months—for pelvic
ultrasound scan to exclude endometrial
hyperplasia
 Refractory symptoms
NICE
All women diagnosed with PCOS should
be screened for metabolic abnormalities
(T2DM, dyslipidemia, hypertension),
regardless of BMI.
All women with suspected PCOS should
be screened for thyroid disease,
hyperprolactinemia, and nonclassical
congenital adrenal hyperplasia.
AAFP July 2016.
NICE September 2012.
RCOG June 2015.

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PCOS

  • 2. F 22 yrs old lady, unmarried, c/o irregular period since 2 yrs. Her period comes every 2-3 months. normal flow , no inter-menstrual bleeding She gained 20kg in the past 18 months.
  • 3. O/E: Obese lady, BMI 30 BP: 125/80 . HR: 75 Grade II acne over her face. Mild fine hair growth , face . Thyroid: normal. Systemic examination normal.
  • 4. Epidemiology and pathophysiology. Clinical manifestation. Diagnosis. Management.
  • 5. PCOS is the most common endocrinopathy among reproductive-aged women in the United States, affecting approximately 7% of female patients. Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745-2749.
  • 6.  Has been linked to altered (LH) action, insulin resistance, and a possible predisposition to hyperandrogenism.  One theory maintains that underlying insulin resistance exacerbates hyperandrogenism by: • suppressing synthesis of sex hormone–binding globulin and • increasing adrenal and ovarian synthesis of androgens, thereby • increasing androgen levels.  These androgens then lead to irregular menses and physical manifestations of hyperandrogenism
  • 7. Hyperandrogenism • Acne, androgenic alopecia, hirsutism • Testosterone, dehydroepiandroster one. Ovulatory dysfunction • Oligoamenorrhea • amenorrhea Polycystic ovary • 12 or more follicles ( or 25 in new US technology ). • Each measuring 2-9 mm • OR ovary volume >10ml.
  • 8. Rotterdam criteria: Diagnosis requires the presence of at least two of the following three findings:  Hyperandrogenism, Ovulatory dysfunction, Polycystic ovaries. ]AAFP and RCOG[
  • 9.  Diagnosis can generally be accomplished with a careful history, physical examination, and basic laboratory testing, without the need for ultrasonography or other imaging. ]AAFP[
  • 10.  PCOS is associated with metabolic syndrome.  About one-half of women with PCOS are obese.  Increase risk of cardiovascular disease.  Fourfold increase in the risk of T2DM.  Increased prevalence of nonalcoholic fatty liver disease, sleep apnea, and dyslipidemia in patients with PCOS, even when BMI is controlled.  Increased risk of mood disorders among patients with PCOS
  • 11.  the American College of Obstetricians and Gynecologists recommend that clinicians evaluate:  blood pressure at every visit,  lipid levels at the time of diagnosis,  screen for T2DM with GTT regardless of a patient’s BMI.  Patients should have repeat diabetes screening every 3-5years, or more often if other indications for screening are present.
  • 12.
  • 13.
  • 14. There is no need to order laboratory testing for these conditions if the patient does not have suggestive physical findings.
  • 15. Not necessary A ratio >2 generally indicates PCOS, but there are no exact cutoff values because many different assays are used. The FSH level is more helpful in ruling out ovarian failure.
  • 16. Anovulation is common after menarche, so it is reasonable to delay workup for PCOS in adolescents until they have been oligomenorrheic for at least two years. If an adolescent is evaluated for PCOS, it has been suggested that she meet all three of the Rotterdam criteria before being diagnosed with the condition.
  • 17. Treatment should be individualized based on the patient’s presentation and desire for pregnancy.
  • 18. Lifestyle modification and weight reduction reduce insulin resistance and can significantly improve ovulation.  Lifestyle modification considered as first- line therapy for women who are overweight. AAFP
  • 19. clomiphene citrate (50–100 mg). Successful in inducing ovulation in 75– 80% of women. Needs Ultrasound monitoring to minimise the 10% risk of multiple pregnancy, and to ensure that ovulation is taking place ]NICE[
  • 20.  The Endocrine Society recommends clomiphene or letrozole (Femara) for ovulation induction. AAFP  Recent studies suggest that letrozole is associated with higher live-birth rates and ovulation rates compared with clomiphene in patients with PCOS. Legro RS, Brzyski RG, Diamond MP, et al.; NICHD Reproductive Medicine Network. Letrozole versus clomiphene for infertility in the polycystic ovary syndrome [published correction appears in N Engl J Med. 2014; 317(15):1465]. N Engl J Med. 2014;371(2):119-129.
  • 21.  The impact of metformin on fertility is controversial; although it was once believed to improve infertility, a 2012 Cochrane review concluded that it does not. AAFP  Metformin alone may improve the rate of ovulation, but results of a large RCT shows that metformin will result in a live birth rate of only 7%. In the same RCT, metformin added to clomiphene conferred no additional benefit in terms of live birth rate compared with clomiphene alone. NICE
  • 22.  In a patient not seeking pregnancy, hormonal contraception is the initial medication for treatment of irregular menses and hyperandrogenism manifesting as acne or hirsutism.  No superiority of one oral contraceptive over another in treating PCOS.  Prevention of endometrial hyperplasia from chronic anovulation may be accomplished by progesterone derivatives.
  • 23. Small studies have shown that metformin can restore regular menses in up to 50% to 70% of women with PCOS, but oral contraceptives have been shown to be superior to metformin for regulating menses and lowering androgen levels Romualdi D, De Cicco S, Tagliaferri V, Proto C, Lanzone A, Guido M. The metabolic status modulates the effect of metformin on the antimullerian hormone-androgens-insulin interplay in obese women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2011;96(5):E821-E824.
  • 24.  According to a 2015 Cochrane review, the most effective first-line therapy for mild hirsutism is oral contraceptives.  Spironolactone, 100 mg daily, and flutamide, 250 mg twice daily, are safe for patient use, but the evidence for their effectiveness is minimal.  Electrolysis, or lasers and intense pulsed light.
  • 25. Hormonal contraceptives are first-line medications for treating acne associated with PCOS, in conjunction with standard topical acne therapy (e.g., retinoids, antibiotics, benzoyl peroxide) or as monotherapy. Antiandrogens, spironolactone can be added as second-line medications.
  • 26.
  • 27.  Serum testosterone >5 nmol/l (to exclude other causes of androgen excess, e.g. tumours, late onset congenital adrenal hyperplasia, Cushing's syndrome)  Infertility  Rapid onset of hirsutism (to exclude androgen secreting tumours)  Glucose intolerance/diabetes  Amenorrhoea of more than 6 months—for pelvic ultrasound scan to exclude endometrial hyperplasia  Refractory symptoms NICE
  • 28. All women diagnosed with PCOS should be screened for metabolic abnormalities (T2DM, dyslipidemia, hypertension), regardless of BMI. All women with suspected PCOS should be screened for thyroid disease, hyperprolactinemia, and nonclassical congenital adrenal hyperplasia.
  • 29. AAFP July 2016. NICE September 2012. RCOG June 2015.