Amenorrhea Symposium Hengameh Abdi Endocrine Research Center Research Institute for Endocrine Sciences Shahid Beheshti University of Medical Sciences 03 January 2019 Tehran Agenda ID: 935966
Download Presentation The PPT/PDF document "Polycystic Ovary Syndrome" is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
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
Slide2AgendaA case vignetteDefinition and diagnosis of PCOS
Normal female reproductive axis
Pathophysiology of PCOS
Conclusions
2
Slide3A 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.
3
Slide4Diagnostic criteria for the PCOSLegro RS, et al. J Clin
Endocrinol
Metab 2013;98(12):4565-4592.4
XX, must be present for diagnosis.
Slide5Rotterdam 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.
5
Slide6Diagnosis 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
6
Slide7Suggested diagnostic criteria for the PCOS in adolescence Báñez L,
et al.
Horm
Res Paediatr 2017; DOI: 10.1159/000479371.7
Slide8Types of abnormal uterine bleeding (AUB) suggestive of abnormal degree of anovulation in adolescent PCOSRosenfield RL. Pediatrics 2015;136(6
):1154-65.
8
Slide9Ovulatory 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.
9
Fritz MA &
Speroff
L.Clinical
Gynecologic Endocrinology and Infertility 8th
ed
2011;495-531.
Slide10Determination 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.
10
Dumesic DA, et al. Endocrine Reviews
2015;36:487-525.
Slide11Progestin 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.
Slide12Can 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.
Slide13AgendaA case vignetteDefinition and diagnosis of PCOS
Normal female reproductive axis
Pathophysiology of PCOS
Conclusions
13
Slide1414Female 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.
Slide15Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.15
Two-cell hypothesis for ovarian
steroidogenesis
in the
preovulatory
follicle
Slide16Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.16
Two-cell hypothesis for ovarian
steroidogenesis
in thecorpus
luteum
Slide17Bulun SE. Williams Textbook of Endocrinology 13th ed 2016;589-663.17
Cyclic changes of the endometrium
Slide18Fritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.18
Slide19Fritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.19
Slide20AgendaA case vignetteDiagnosis of PCOS
Normal female reproductive axis
Pathophysiology of PCOS
Conclusions
20
Slide21Normal menstrual cycleFritz MA & Speroff L.Clinical Gynecologic Endocrinology and Infertility 8th ed 2011;495-531.
21
Chronic anovulation
Slide22Complex 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
22
Slide23McCartney CR, Marshall JC. N Engl J Med 2016;375:54-64.23
Slide2424A: Androstenedione, T: Testosterone, DHT: Dihydrotestosterone; Numbers are indicative of descending order of serum concentrations of androgens.
1
2
3
4
5
Androgen biosynthesis in women
Bulun
SE. Williams Textbook of Endocrinology 13th
ed
2016;589-663.
PCOS
PCOS
Slide25Androgen excess in the PCOSMcCartney CR, Marshall JC. N Engl J Med 2016;375:54-64.
25
Slide26Pathophysiological heterogeneity in PCOSEscobar-Morreale HF. Nat. Rev. Endocrinol 2018;14(5):270-284.
26
Slide27PCOS 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.
27
Dumesic DA, et al. Endocrine Reviews
2015;36:487-525.
Slide28Conclusions
Slide29The heterogeneous nature of PCOSEscobar-Morreale HF. Nat. Rev. Endocrinol 2018;14(5):270-284.
29
Slide30Thanks for your attention.Photo by Majid
Valizadeh
, MD.30