Polycystic Ovary Syndrome - PowerPoint Presentation

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Polycystic Ovary Syndrome(Amenorrhea Symposium)

Hengameh

Abdi

Endocrine Research Center

Research Institute for Endocrine

Sciences

Shahid

Beheshti

University of Medical Sciences

03 January 2019

Tehran

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AgendaA case vignetteDefinition and diagnosis of PCOS

Normal female reproductive axis

Pathophysiology of PCOS

Conclusions

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A case vignetteA 22-year-old woman reports having hirsutism and irregular menses. She describes unpredictable and infrequent menses (5-6 per year) since menarche at 11

years of

age. Dark, coarse facial hair began to develop at 13 years of

age. The symptoms worsened after she gained weight in college.

Physical examination:

BMI: 29 kg/m²

Blood pressure: 135/85 mm HgModerate hirsutism without virilization.

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Diagnostic criteria for the PCOSLegro RS, et al. J Clin

Endocrinol

Metab 2013;98(12):4565-4592.4

XX, must be present for diagnosis.

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Rotterdam criteria to document PCO morphologyAt least one ovary with 12 follicles of 2-9 mm or a volume > 10

mL in the absence of a dominant follicle

> 10 mm.

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Diagnosis after exclusion of:Other causes of chronic anovulation:Thyroid disordersHyperprolactinemia

Pregnancy

Hypothalamic amenorrhea

Primary ovarian insufficiencyOther causes of androgen excess:Nonclassical congenital adrenal hyperplasia

Idiopathic hirsutism/Idiopathic

hyperandrogenism

Androgen-secreting tumorSevere insulin resistance syndromesCushing syndromeAcromegaly

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Suggested diagnostic criteria for the PCOS in adolescence Báñez L,

et al.

Horm

Res Paediatr 2017; DOI: 10.1159/000479371.7

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Types of abnormal uterine bleeding (AUB) suggestive of abnormal degree of anovulation in adolescent PCOSRosenfield RL. Pediatrics 2015;136(6

):1154-65.

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Ovulatory and menstrual dysfunction in the PCOSNormal cyclic menses result from normal ovulatory function

. The

normal

inter-menstrual interval ranges between 24 and 35 days and menses that occur less or more often are an indication of ovulatory dysfunction. Cyclic menses occurring at normal intervals strongly suggest

, but cannot be regarded as proof of ovulation.

60-85% of

women with PCOS exhibit gross menstrual dysfunction: The most common abnormalities: oligomenorrhea

and

amenorrhea.

Polymenorrhea

is

very

uncommon (< 2%).

Classically

, menstrual

dysfunction in

women with PCOS has a

premenarcheal

onset, but many report regular

cycles for

varying intervals preceding the onset of

oligo

/amenorrhea.

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Fritz MA &

Speroff

L.Clinical

Gynecologic Endocrinology and Infertility 8th

ed

2011;495-531.

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Determination of chronic anovulationWomen with regular menstrual cycles may have chronic

anovulation.

To confirm

anovulation, clinicians may obtain a serum progesterone

level

during the suspected

mid-luteal phase of the cycle and presume that the cycle is oligo-anovulatory if the level is < 3-4 ng/mL.

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Dumesic DA, et al. Endocrine Reviews

2015;36:487-525.

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Progestin challenge testMedroxyprogesterone acetate 5-10 mg/day orally for 10 days:Because

endometrium

is exposed

to estradiol chronically in PCOS, these women respond to the challenge and uterine bleeding will occur within a few days (2-7 days) after the last pill of progestin.

The

overall correlation between withdrawal bleeding and estrogen status

is far from perfect and both false positive and false negative results are relatively common:Up to 20% of amenorrheic women with significant estrogen production have no withdrawal bleeding.

11

Fritz MA &

Speroff

L.Clinical

Gynecologic Endocrinology and Infertility 8th

ed

2011;495-531

.

Bulun

SE. Williams Textbook of Endocrinology 13th

ed

2016;589-663.

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Can PCOS present with primary amenorrhea?The reported percentage

of primary amenorrhea

as an initial feature in PCOS

among small cohorts has varied between 1.4% and 14%.

Adolescents with primary amenorrhea and PCOS exhibit

increased features

of the metabolic syndrome and higher androstenedione levels and may represent a more severe spectrum of a common condition.12

Rachmiel

M,

et al. Arch

Pediatr

Adolesc

Med. 2008;162(6):

521-525.

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AgendaA case vignetteDefinition and diagnosis of PCOS

Normal female reproductive axis

Pathophysiology of PCOS

Conclusions

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14Female reproductive axis

More rapid

GnRH

pulse

frequencies favor LH

secretion, whereas

slower pulse frequencies favor FSH.Estradiol increases GnRH pulse frequency, and elevated progesterone levels decrease GnRH pulsatility.

GnRH

,

gonadotropin-releasing hormone; LH, luteinizing hormone; FSH,

follicle-stimulating hormone.

Dumesic

DA, et al

. Endocrine

Reviews 2015;36:487-525.

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Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.15

Two-cell hypothesis for ovarian

steroidogenesis

in the

preovulatory

follicle

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Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.16

Two-cell hypothesis for ovarian

steroidogenesis

in thecorpus

luteum

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Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.17

Cyclic changes of the endometrium

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Fritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.18

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Fritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.19

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AgendaA case vignetteDiagnosis of PCOS

Normal female reproductive axis

Pathophysiology of PCOS

Conclusions

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Normal menstrual cycleFritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.

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Chronic anovulation

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Complex pathophysiology of PCOS Disordered gonadotropin secretionIncrease in mean LH

levels

and

in LH pulse frequency and amplitude; FSH levels may be normal or low.Hyperandrogenism

Insulin

resistance

and hyperinsulinemiaOvarian dysfunction and follicular arrest

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McCartney CR, Marshall JC. N Engl J Med 2016;375:54-64.23

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24A: Androstenedione, T: Testosterone, DHT: Dihydrotestosterone; Numbers are indicative of descending order of serum concentrations of androgens.

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2

3

4

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Androgen biosynthesis in women

Bulun

SE. Williams Textbook of Endocrinology 13th

ed

2016;589-663.

PCOS

PCOS

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Androgen excess in the PCOSMcCartney CR, Marshall JC. N Engl J Med 2016;375:54-64.

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Pathophysiological heterogeneity in PCOSEscobar-Morreale HF. Nat. Rev. Endocrinol 2018;14(5):270-284.

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PCOS and endometrial cancer riskRisk factors for endometrial cancer in women with

PCOS:

- obesity - metabolic abnormalities (such as diabetes and hypertension)

-

prolonged

exposure to unopposed estrogenWomen with PCOS have a 2.7-fold increased risk for developing endometrial cancer vs the general population. This increased endometrial cancer

risk in PCOS likely

applies to a subgroup

of PCOS women with obesity

, because the risk is reduced but not

eliminated when

adjusted for

BMI.

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Dumesic DA, et al. Endocrine Reviews

2015;36:487-525.

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Conclusions

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The heterogeneous nature of PCOSEscobar-Morreale HF. Nat. Rev. Endocrinol 2018;14(5):270-284.

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Thanks for your attention.Photo by Majid

Valizadeh

, MD.30