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Pcos ve amh 20140930
- 1. SŞ Prof.Dr.Sezai ŞAHMAY İ.Ü.Cerrahpaşa Tıp Fakültesi Kadın hastalıkları ve Doğum ABD Üreme Endokrinolojisi ve İnfertilite Bilim Dalı Başkanı www.jinekolojik.org www.sahmay.com
- 2. SŞ PKOS tanısı önemlidir • PKOS, çok sayıda fenotipe sahiptir, • Net ve kesin tarifi gereklidir, • İnfertilite, Kanama düzensizlikleri (AUB), obesite, metabolik sendrom, endometrial kanser, • PKOS yaşam boyu takip gerektirir, • Hastalığın tanı ve şiddetini gösteren objektif bir belirtece ihtiyaç vardır.
- 3. SŞ Yaşam boyu Hiperandrojenism İntrauterin Düşük Doğum Ağırlığı Prepubertal Prematüre pubarş Adolösan Fonksiyonel ovaryan HA Erişkin PKOS İleri yaş Metabolik sendrom Blume Peytavi U et al.:Hair growth and disorders, Springer, Berlin, 2008
- 4. SŞ PKOS tanısında 3 bulgu 1. Hiperandrogenism 2. Oligo/Amenore 3. USG’de Polikistik Over Morfolojisi (PKOM)
- 5. SŞ 1. Hiperandrojenism Bulguları • Hiperandrojenemi Androjen fazlalığı, PKOS’lu hastaların %60-80’ninde görülür. En sık artan androjen Serbest Testosterondur. • Hirsutism Hiperandrojenismin en sık rastlanan (%60-70) klinik bulgusudur. FG>6 (3-8?) • Akne Özellikle genç PKOS’lu hastaların 1/3’nde görülür. • Alopesi Vertekste kıllanmanın azalmasıdır. Az rastlanan bir semptomdur. (%5)
- 6. SŞ Hiperandrojenism semptomları Siklus Boz. 45,4 Hirsutism 40 Akne 13,3 Sebore 15,8 Alopesi 9,8 Siklus Boz. Hirsutism Akne Sebore Alopesi Sahmay S, Atakul N ve ark, Baskıda
- 8. SŞ PKOS’da Hiperandrojenemi ve Hirsutism 29.26 3.44 3.88 74.69 Sales Total T Free T DHEAS Hirsutim Azziz R et al.: Fertil Steril 91,: 2009
- 9. SŞ 2. Oligo-Amenore (Kronik anovülasyon) • PKOS’da genellikle anovülasyon sonucu, oligo- amenore görülür. <8 siklus/yıl veya >35gün. • Menstrüel düzensizlik (oligo/amenore) oranı %75 dir. • PKOS’da regüler sikluslarda dahi ovülatuar disfonksiyon söz konusu olabilir. (subklinik oligo/anovülasyon) • Kronik anovülasyon, PKOS tanısında temel bulgudur.
- 10. SŞ • Folikül sayısı >12 • Folikül boyutu 2-9mm. • İri Yumurtalık (Over hacmi >10cm3) stroma Ultrasonografide Yumurtalığın tipik POLİKİSTİK Görünümü 3. Polikistik Over Morfolojisi (PKOM) USG’de PKOM görünümü %22 <35, %8 >35 PKOM (PoliKistik Over Morfolojisi) tanımı
- 11. SŞ PCOS – Tanı Kriterleri NIH (1990) Rott (2003) AES (2006) Hyperandrojenism + +/- + Oligo/amenore + +/- +/- PKOM (USG) +/- +/- Hiperandrojenisme neden olan bir başka etkenin olmaması.
- 12. SŞ PKOS Fenotipler (Semptom ve tariflere göre) Kopera D et al.:Int J Trichology 2:30, 2010 Goodarzi MO et al.:Nat. Rev. Endocrinol. 7:219, 2011 Azziz R et al.: Fertil Steril 91,: 2009
- 13. SŞ Tehrani FR et al.:Reproductive Biology and Endocrinology , 9:39, 2011 8 8.3 10.9 0 2 4 6 8 10 12 7.1 11.7 14.6 0 2 4 6 8 10 12 14 16 NIH AES Rott Prevalence of PCOS using different definition Prevalence of HA
- 14. SŞ Primer ve küçük antral foliküllerden salgılanır. Granülosa hücreleri salgılar. FSH ile etkileşimi yok veya çok azdır. Overin foliküler yapısının tek markörüdür. Visser, J. A. et al. Nat. Rev. Endocrinol 10:331, 2012 Antimüllerien Hormon (AMH) Müllerien Inhibiting Sustance (MIS) Müllerien Inhibiting Hormone (MIH) Prof.Albert Jost 1947 - MIH
- 15. SŞ AMH ve PKOS ilişkisi - 1 • AMH yüksekliği; antral folikül sayısının artışı ve/veya granülosa hücrelerinin AMH sekresyon artışından kaynaklanır Wang et al., 2007, Mulders et al., 2004 • PKOS’lu kadınların foliküler sıvılarında AMH düzeyi daha yüksektir. Das et al., 2008 • AFC ve serum AMH düzeyleri paralel seyreder. Thaı´s S. Et al. 2010 • AMH’nın androjen düzeyi ile pozitif korelasyonu söz konusudur. Pigny et al. 2003, Laven et al. 2004, Eldar-Geva et al. 2005 • PKOS’lu kadınlarda serum AMH düzeyleri ile LH düzeyi ilişkilidir. Luciano G et al. 2009, Neoklis A. Et al. 2010
- 16. SŞ • AMH düzeyi, PKOS ana fenotipleri ile ilişkilidir. La Marca et al., 2004; Pigny et al., 2006 • AMH düzeyi , PKOS şiddeti ile paralel seyreder. Fleming et al., 2006 • PKOS tanısında, antral folikül sayısı yerine AMH ölçümü kullanılabilir. Pigny et al., 2006 • AMH’nın PKOS tanısında iyi bir belirteç olabileceği vurgulanmaktadır. La Marca and Volpe A, 2006 AMH ve PKOS ilişkisi - 2
- 17. SŞ Sahmay S, Guralp O et al.:Reprod Med Biol. 10:113, 2011 PKOS ve nonPKOS’da VKİ ve AMH düzeyi
- 18. SŞ 6.85 2.27 6.66 2.28 0 1 2 3 4 5 6 7 8 PCOS nPCOS BMI<25 BMI>25 BMI does’nt effect on serum AMH levels in women with and without PCOS. AMH (ng/ml) Sahmay S, Guralp O et al.:Reprod Med Biol. 10:113, 2011
- 19. SŞ PKOS tanısında artmış AMH düzeyi Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 20. SŞ 7,34 2,24 PCOS (n.419) Control PKOS’nda serum AMH düzeyi PKOS’nda artmış serum AMH düzeyi folikül sayısı artışının yanında foliküler üretimin de artışındandır. Kontrol (n.151) Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 21. SŞ AUC=0,916 3,79 81,1 86,3 3,94 80,0 89,8 4,19 77,1 91,4 Cut-off Sens. Spes. PKOS tanısında serum AMH sınır değeri Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 22. SŞ Yaş gruplarına göre PCOS ve nonPCOS’ta AMH değerleri Age of PCOS Age of Control p (Age) AMH- PCOS (ng/ml) AMH- Control (ng/ml) p (AMH) 35-40 years 36.4±1.6 (n=29) 37.0±1.4 (n=130) 0.06 5.4±2.2 1.7±1.3 0.001 29-34 years 31.1±1.6 (n=99) 31.3±1.6 (n=143) 0.17 6.8±3.4 2.3±1.6 0.001 23-28 years 25.4±1.7 (n=174) 26.1±1.5 (n=83) 0.01* 7.6±4.1 2.7±1.8 0.001 17-22 years 19.4±1.9 (n=117) 19.9±1.3 (n=16) 0.31 7.8±4.5 3.9±2.5 0.001 Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 23. SŞ PKOS`de AMH düzeyi anlamlı olarak yüksektir Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 24. SŞ AMH Percentile – PCOS oranı Düşük AMH değerlerinde PCOS olasılığı cok azdır. Sahmay S, Atakul N et al.: Acta Obstet Gynecol Scand. 2013 Dec;92(12):1369-74. doi: 10.1111/aogs.12247. Epub 2013 Oct 15.
- 25. SŞ PKOS ana fenotiplerinde AMH düzeyi Sahmay S, Atakul N, Oncul M, Tuten A, Aydogan B, Seyisoglu H.. Eur J Obstet Gynecol Reprod Biol. 2013, 170(1):157-61
- 26. SŞ PKOS şiddeti AMH düzeyi ile ilşkilidir (n.276) Patient number (%) Age BMI (kg/m2) AMH (ng/ml) FSH (Iu/L) LH (Iu/L ) E2 (pml/l) DHEAS (nmol/l) 17-OHP (nml/l) Total T (nmol/l) Free T (nmol/l) PCOM+/OA+/HA+ 119 (22,2 24,73 26,16 9,50 4,50 5,86 41,23 358,97 1,89 110,46 2,39 PCOM+/OA+/HA- 61 (11,4) 24,77 25,02 8,02 4,77 5,65 35,18 348,43 1,15 108,38 3,28 PCOM+/OA-/HA+ 45 (8,4) 24,73 25,25 6,12 5,62 4,86 37,39 358,31 1,60 114,52 2,08 PCOM+/OA-/HA- 25 (4,7) 27,04 25,37 5,52 5,62 4,18 43,80 292,71 1,22 102,85 1,71 PCOM-/OA+/HA+ 26 (4,8) 23,12 27,57 3,06 4,46 3,72 29,60 350,12 2,42 102,09 3,56 Sahmay S, Atakul N, Oncul M, Tuten A, Aydogan B, Seyisoglu H.. Eur J Obstet Gynecol Reprod Biol. 2013, 170(1):157-61
- 27. SŞ PKOS şiddeti AMH düzeyi ile ilşkilidir (n.276) Patient number (%) Age BMI (kg/m2) AMH (ng/ml) FSH (Iu/L) LH (Iu/L ) E2 (pml/l) DHEAS (nmol/l) 17-OHP (nml/l) Total T (nmol/l) Free T (nmol/l) PCOM+/OA+/HA+ 119 (22,2 24,73 26,16 9,50 4,50 5,86 41,23 358,97 1,89 110,46 2,39 PCOM+/OA+/HA- 61 (11,4) 24,77 25,02 8,02 4,77 5,65 35,18 348,43 1,15 108,38 3,28 PCOM+/OA-/HA+ 45 (8,4) 24,73 25,25 6,12 5,62 4,86 37,39 358,31 1,60 114,52 2,08 PCOM+/OA-/HA- 25 (4,7) 27,04 25,37 5,52 5,62 4,18 43,80 292,71 1,22 102,85 1,71 PCOM-/OA+/HA+ 26 (4,8) 23,12 27,57 3,06 4,46 3,72 29,60 350,12 2,42 102,09 3,56 Sahmay S, Atakul N, Oncul M, Tuten A, Aydogan B, Seyisoglu H.. Eur J Obstet Gynecol Reprod Biol. 2013, 170(1):157-61
- 28. SŞ AMH düzeyinin PKOM ve OA ile ilişkisi Sahmay S , Aydın Y, et al.:Gynecol Endocrinol. 2014 Feb;30(2):130-4 doi: 10.3109/09513590.2013.867320. Epub 2013 Dec 16. Serum AMH düzeyi, PKOM ve siklus düzeni ile sıkı ilişkilidir, Buna karşılık, hirsutism ve androjenik hormonlarla ilişki değildir.
- 29. SŞ AMH’nın klinik olarak HA ile ilişkisi Sahmay S , Aydın Y, et al.:Gynecol Endocrinol. 2014 Feb;30(2):130-4 doi: 10.3109/09513590.2013.867320. Epub 2013 Dec 16.
- 30. SŞ PKOS tanısında AMH ve klinik semptom kombinasyonu Sahmay S, Aydın Y, Oncul M, Senturk LM: J Assist Reprod Genet. 2014 Feb;31(2):213- 20. doi: 10.1007/s10815-013-0149-0. Epub 2013 Dec 18.
- 31. SŞ PKOS, PKOM ve Normal Overlerde AMH 10,86 ng/ml 7,31 ng/ml 3,30 ng/ml Homburg R. Et al.:Hum Reprod 2013;28:1077-1083.
- 32. SŞ Dewailly et al.:J Clin Endocrinol Metab, 95:4399, 2010 PKOS tanısında kullanılan klasifikasyonlara AMH adaptasyonu
- 33. SŞ PKOS tanısında AMH ve klinik bulgular Dewailly D, Gronier H et al.:Human Reproduction, Vol.26, No.11 pp. 3123–3129, 2011
- 34. SŞ • AMH, Primer ve küçük antral foliküllerden salgılanır, • Overin foliküler yapısının önemli bir markörüdür, • AMH yüksekliği; AFS artışı ve/veya granülosa hücrelerinin AMH sekresyonu artışından kaynaklanır, • PKOS’lu hastalarda, serum AMH düzeyi 2-3 kat daha yüksektir, • AMH stabil bir belirteç olup, tek ölçüm yeterlidir, • AMH düzeyi, PKOS şiddeti ile de paralellik göstermektedir, • AMH, PKOS tanı ve klasifikasyonunda yeni bir belirteçdir. Özet
- 35. SŞ Bir ülkede yalakalığın getirisi, dürüstlüğün getirisinden daha fazla ise, o ülke batar. MONTESQUİEU İlim Ve Sanat, İlgi Görmediği Yerden Göç Eder. İBNİ SİNA Alçak Olan Kimse Düşmekten Korkmaz. ARİSTO
- 36. SŞ
Editor's Notes
- Diagnostic Criteria for Polycystic Ovary Syndrome: Pitfalls and Controversies. J Obstet Gynaecol Can. 2008 August ; 30(8): 671–679. EVALUATING ANDROGEN EXCESS Hyperandrogenemia: It is estimated that 60% to 80% of women with PCOS demonstrate elevated circulating androgen levels. Serum levels of free testosterone, and not total testosterone, are more frequently elevated in women with PCOS. Hirsutism: Hirsutism is the most common clinical manifestation of hyperandrogenism in women. Approximately 60% to 70% of women with PCOS have hirsutism. Scores of ≥ 8 or ≥ 5 have been commonly accepted as abnormal,44,45 although recently a score as low as 3 was proposed as the upper limit of normal. Acne: One third of women with PCOS, particularly younger women, demonstrate acne Alopecia: Women may experience a diffuse pattern of thinning hair over the vertex of the scalp with the frontal hairline commonly preserved While the actual prevalence of alopecia in women with PCOS is relatively low compared with other androgenic symptoms (approximately 5%),
- Investigating hirsutism- T Sathyapalan,1 Stephen L Atkin2 - BMJ 2009;338:912 The most common causes of clinical hyperandrogenism are PCOS (72%), idiopathic (no other clinical or biochemical abnormalities) hyperandrogenism (23%), non-classic adrenal hyperplasia (4.3%), and androgen secreting tumours (0.2%).2 A high total testosterone concentration indicates that hyperandrogenaemia may be caused by an ovarian or adrenal tumour.
- Diagnostic Criteria for Polycystic Ovary Syndrome: Pitfalls and Controversies. J Obstet Gynaecol Can. 2008 August ; 30(8): 671–679. EVALUATING ANOVULATION Menstrual disturbances in PCOS generally present in the form of oligo-amenorrhea (fewer than eight episodes of menstrual bleeding per year or menses that occur at intervals greater than 35 days).27 Menstrual irregularity in women with PCOS is primarily the consequence of anovulation. Ovulatory dysfunction may be present in women with PCOS who report regular menstrual cycles.
- Diagnostic Criteria for Polycystic Ovary Syndrome: Pitfalls and Controversies. J Obstet Gynaecol Can. 2008 August ; 30(8): 671–679. EVALUATING POLYCYSTIC OVARIAN MORPHOLOGY The current ultrasonography guidelines, supported by the ESHRE/ASRM consensus group, define the polycystic ovary as containing 12 or more follicles measuring 2–9 mm and/or an increased ovarian volume of > 10 cm3.
- (1) PCO morphology: PCO morphology was defined as ≥1 ovary with a volume .10 cm3 or 12 or more follicles between 2 and 9 mm diameter (Balen et al., 2003). (2) Hyperandrogenism: Clinical HA was defined by a F-G score of ≥8 (Ferriman and Galwey, 1961; van Hooff et al., 1999a,b; Azziz et al., 2004). Biochemical HA was defined as the top fifth percentile for calculated early follicular phase cFT levels (Huang et al., 2010). (3) Oligo-anovulation: Ovulation was determined using menstrual cycle regularity, prospectively measured using a purpose-designed menstrual diary over 90 days. Irregular cycles were defined as those ,21 or .35 days in duration or where the cycle length varied from month to month by .4 days (Treloar, 1981). Other causes of oligo-anovulation were excluded by measuring TSH and prolactin concentrations. Clinical, ultrasound and biochemical features of polycystic ovary syndrome in adolescents: implications for diagnosis. M. Hickey1,*, D.A. Doherty2, H. Atkinson2, D.M. Sloboda3, S. Franks4, R.J. Norman5, and R. Hart2. Human Reproduction, Vol.26, No.6 pp. 1469–1477, 2011 --------------------------------------------------------- Many asymptomatic volunteers have a PCO. They are a distinct, but heterogeneous, population with respect to ovarian function, ranging from normal (53%) to occult PCOS by Rotterdam criteria (25%). Nearly one quarter (22%) had the typical PCOS type of ovarian dysfunction without hyperandrogenemia, termed a “dysregulated PCO”; they or their offspring may be at risk for PCOS. Ovarian ultrasonographic characteristics must be considered when establishing norms for ovarian function. (Asymptomatic Volunteers with a Polycystic Ovary Are a Functionally Distinct but Heterogeneous Population---J Clin Endocrinol Metab 94: 1579–1586, 2009)
- Phenotypes of PCOS based on various symptoms and definitions (NIH, Rotterdam und AE-PCOSCriteria) The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Ricardo Azziz, M.D., M.P.H.,a Enrico Carmina, M.D.,b Didier Dewailly, M.D.,c Evanthia Diamanti-Kandarakis, M.D.,d Hector F. Escobar-Morreale, M.D., Ph.D.,e Walter Futterweit, M.D.,f Onno E. Janssen, M.D.,g Richard S. Legro, M.D.,h Robert J. Norman, M.D.,i Ann E. Taylor,j and Selma F. Witchel, M.D.,k (Task Force on the Phenotype of the Polycystic Ovary Syndrome of The Androgen Excess and PCOS Society*) Fertility and Sterility Vol. 91, No. 2, February 2009 Women with Clinical Hyperandrogenism Clinically hyperandrogenism can manifest itself in the form of unwanted hair growth or hirsutism, seborrhea, and/or acne, and androgenic alopecia or male pattern balding. Alternatively, clinical experience has indicated that virilization (i.e., masculinization of body musculature, severe or extreme male-pattern balding or hirsutism, clitoromegaly, and so forth) is rarely a sign of PCOS. Hyperandrogenemia Hyperandrogenemia refers to the finding of supranormal levels or estimates of circulating endogenous androgens. The most frequent androgen measured is testosterone (T), total, unbound, or free. Androstenedione (A4) and dehydroepiandrosterone (DHEA), and the DHEA metabolite DHEAS, may also be measured. cutoff values for defining hirsutism have been variously reported to be a score of 6 or greater (6), 7 or more (150), and 8 or more (149). Acne affects approximately 12% to 14% of White PCOS patients (10, 47, 152) although the prevalence of this dermatologic abnormality varies with ethnicity. Overall, although acne affects 15% to 25% of PCOS patients,it is unclear whether the prevalence of acne is significantly increased in these patients over that observed in the general population. Prevalence of alopecia in PCOS vary widely, from 5% to 50%, and further studies are needed to better define this prevalence. The prevalence of polycystic ovaries appears to be relatively high among patients with androgen excess or PCOS (Table 4) (86, 88, 89, 92, 93, 95, 97, 99, 110, 168, 175, 176). In a study of 173 women with anovulation or hirsutism, polycystic ovaries by ultrasound was found in 92% of women with hirsutism with regular menstrual cycles, 87% of women with oligomenorrhea, 57% of anovulatory women, and 26% of women with amenorrhea (12). Using transvaginal ultrasound, 60% of 226 women with PCOS diagnosed by NIH criteria had increased ovarian size and another 35% had polycystic ovaries with normal ovarian size (171). Gonadotropic abnormalities (LH/FSH) increased secretion of LH, resulting from an accelerated GnRH/LH pulse frequency, whereas FSH levels are normal or even decreased. Adequate studies using frequent blood sampling and accurate gonadotropin assays demonstrate that >75% of PCOS patients present with a dysregulation in gonadotropic function (177–179). lean PCOS women that primarily have an increased LH pulse amplitude, explaining in part the finding that in many obese women with PCOS basal LH levels are within the normal range and the ratio of LH to FSH is not increased (84). the increased secretion of LH, and an increase in the ratio of serum LH to FSH during the follicular phase of the menstrual cycle, has been considered as a marker of PCOS (180). For the reasons outlined above, basal gonadotropin measurements are not generally helpful for the diagnosis of PCOS. Overall, between 50% and 70% of women with PCOS have demonstrable insulin resistance. 50% of women with PCOS are obese. Hyperprolactinemia is a frequent cause of amenorrhea and infertility in clinical endocrinology and has been found in up to 30% of women with secondary amenorrhea. In summary, some hyperandrogenic patients, possibly as high as 3%, suffer from the HAIR-AN syndrome, primarily characterized by extreme degrees of insulin resistance and hyperinsulinism. Patients also exhibit extensive acanthosis nigricans and may also demonstrate varying degrees of lipodystrophy. These patients should be distinguished from women with PCOS, a disorder that is also associated with insulin resistance, although to a much lesser degree than that of patients with the HAIR-AN syndrome. Diagnosis can be achieved by measuring fasting or postprandial insulin levels. Using the NIH 1990 criteria for PCOS, idiopathic hirsutism (IH) can be strictly defined as the presence of hirsutism, in the presence of regular ovulation and in the absence of hyperandrogenemia (294). Using this definition approximately 5% to 7% of hirsute patients will have IH (46, 47, 91, 107). Using the Rotterdam 2003 criteria IH patients have the above features and including the absence of polycystic ovaries. Undoubtedly this will reduce the prevPractically speaking, IH is a diagnosis of exclusion, as is PCOS, and often it is difficult to fully differentiate the two disorders. The diagnosis of IH requires assessment of androgen levels, and it is assumed that some or all of women with IH demonstrate excessive 5a-reductase activity of the hair follicle, which results in hirsutism despite ‘‘normal’’ circulating androgens (295). In evaluating the hirsute apparently eumenorrheic patient for IH (or PCOS) it is also critical to confirm the presence of normal ovulatory function (e.g., by using a basal body temperature chart and/or luteal progesterone measurements). Up to 40% of these individuals are actually oligo-ovulatory if studied more carefully (46, 47, 91,107, 296).alence of IH further.
- Estimated prevalence of idiopathic hirsutism was 10.9% (95% CI: 8.9-12.9%); 8.3% of women had only oligo/anovulation and 8.0% had only polycystic ovaries. The prevalence of PCOS was 7.1% (95% CI: 5.4-8.8%) using the NIH definition, 11.7% (95% CI: 9.5-13.7%) by AES criteria and 14.6% (95% CI: 12.3-16.9%) using the Rott definition.
- Anti-Müllerian hormone: an ovarian reserve marker in primary ovarian insufficiency Jenny A. Visser, Izaäk Schipper, Joop S. E. Laven and Axel P. N. Themmen Visser, J. A. et al. Nat. Rev. Endocrinol. advance online publication 10 January 2012; doi:10.1038/nrendo.2011.224 Nat Rev Endocrinol. 2012 Jan 10;8(6):331-41. ------------------------------------------------------------ Folliculogenesis—the process of follicle maturation from the primordial follicle to the ovulatory follicle. Follicles are continuously recruited from the dormant primordial follicle pool, the so-called initial recruitment, into the growing follicle pool and start to express AMH and inhibin B. After puberty, at every new cycle, a limited number of follicles is selected from this pool of small, growing follicles under the influence of FSH, the so-called cyclic recruitment. From this smaller cohort of growing follicles, ultimately one follicle is selected for dominance and ovulates under the influence of LH.52 The majority of growing follicles is removed through atresia, a hormonally controlled apoptotic process.143 To rescue follicles from atresia, FSH levels need to rise to a critical threshold concentration to allow FSH-dependent selection of a limited number of follicles. As a consequence of the continuous decline in primordial follicles throughout reproductive life, the number of growing follicles also decreases. Subsequently, serum inhibin B and estradiol levels decline, releasing the negative feedback on the hypothalamus and pituitary, which results in the characteristic menopausal monotropic rise in FSH and to a lesser extent in LH levels.64 Abbreviations: AMH, anti-Müllerian hormone; FSH, follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.
- Purpose To evaluate the correlation between anti-mu¨llerian hormone (AMH) and body mass index (BMI) in patients with and without polycystic ovarian syndrome (PCOS). Methods Serum AMH levels of 332 women in their reproductive period and below 45 years of age who were admitted to our reproductive endocrinology clinic with infertility were investigated in a cross-sectional study. Patients were divided into two groups as BMI under and equal or over 25 kg/m2. Both groups were divided into two subgroups as PCOS and non-PCOS. AMH levels of patients were analyzed for each group. Results Mean AMH values of BMI\25 and C25 kg/m2 groups were 3.87 ± 2.95 and 3.58 ± 2.93 ng/mL, respectively (P[0.05) in all patients. Means of AMH were not significantly different in BMI quartiles (r = -0.008401, P = 0.96). Among 107 patients with PCOS, means of AMH were 6.85 ± 2.95 ng/mL in 56 patients with BMI \25 kg/m2 and 6.66 ± 3.18 ng/mL in 51 patients with BMI C25 kg/m2 (P[0.05). In the group of 225 non- PCOS patients, means of AMH were 2.27 ± 1.12 ng/mL in 104 patients with BMI\25 kg/m2 and 2.28 ± 1.49 ng/mL in 121 patients with BMI C25 kg/m2 (P[0.05). Conclusions Body mass index does not seem to have an effect on serum AMH levels in reproductive age women both with and without PCOS.
- Acta Obstet Gynecol Scand. 2013 Aug 28. doi: 10.1111/aogs.12247. [Epub ahead of print] Elevated serum levels of anti-Müllerian hormone can be ıntroduced as a new diagnostic marker for polycystic ovary syndrome. Sahmay S, Atakul N, Aydogan B, Aydın Y, Imamoglu M, Seyisoglu H. Source Subdivision of Reproductive Endocrinology, Department of Obstetrics,Gynaecology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul. Abstract OBJECTIVE: To determine the possible role of anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) with a larger population of patients and to evaluate its role as a new diagnostic marker. DESIGN: Cross sectional study. SETTING: University hospital. POPULATIONS: A total of 570 patients, with PCOS (n=419) and without PCOS (n=151). METHODS: Serum basal hormone (AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH) levels were measured. Mean hormone levels were compared and the predictive value of serum AMH level was evaluated with the use of the receiver operating characteristic (ROC) curve analysis. RESULTS: No statistically significant differences found between PCOS patients and control groups in terms age, body mass index and TSH levels. Differences between mean serum, FSH, LH and estradiol levels and LH/FSH ratio is found to be statistically significant (p< 0.001). Mean serum AMH level was higher in PCOS patients than in controls (7.34 vs 2.24ng/mL, p<0.001). The area under the ROC curve assay yielded a satisfactory result of 0.916 (95% confidence interval 0.897-0.935, p<0.0001). The best compromise between 89,8% specificity and 80% sensitivity was obtained with a cut-off value of 3.94 ng/ml for PCOS diagnosis. CONCLUSIONS: Serum AMH measurement is very valuable in diagnosis of PCOS patients. The serum AMH level in women with hyperandrogenism, or oligo-anovulation could indicate the diagnosis of PCOS when reliable ultrasonography data are not available or when typical clinical and laboratory findings do not exists. The serum AMH level is a new and useful diagnostic tool in PCOS diagnosis. This article is protected by copyright. All rights reserved.
- Serum AMH levels have been found to be significantly increased in PCOS compared with healthy women. Figure 2 Box-and-whisker plots showing the values of serum AMH (1.8 ng/ml _ 10.8 ng/l) (n=164) and in controls (n =74). Horizontal small bars represent the 10–90th percentile range, and the boxes indicate the 25th-75th percentile range. The horizontal line in each box corresponds to the median. Average AMH .... in PCOS, and ............ in control. Acta Obstet Gynecol Scand. 2013 Aug 28. doi: 10.1111/aogs.12247. [Epub ahead of print] Elevated serum levels of anti-Müllerian hormone can be ıntroduced as a new diagnostic marker for polycystic ovary syndrome. Sahmay S, Atakul N, Aydogan B, Aydın Y, Imamoglu M, Seyisoglu H. Source Subdivision of Reproductive Endocrinology, Department of Obstetrics,Gynaecology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul. Abstract OBJECTIVE: To determine the possible role of anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) with a larger population of patients and to evaluate its role as a new diagnostic marker. DESIGN: Cross sectional study. SETTING: University hospital. POPULATIONS: A total of 570 patients, with PCOS (n=419) and without PCOS (n=151). METHODS: Serum basal hormone (AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH) levels were measured. Mean hormone levels were compared and the predictive value of serum AMH level was evaluated with the use of the receiver operating characteristic (ROC) curve analysis. RESULTS: No statistically significant differences found between PCOS patients and control groups in terms age, body mass index and TSH levels. Differences between mean serum, FSH, LH and estradiol levels and LH/FSH ratio is found to be statistically significant (p< 0.001). Mean serum AMH level was higher in PCOS patients than in controls (7.34 vs 2.24ng/mL, p<0.001). The area under the ROC curve assay yielded a satisfactory result of 0.916 (95% confidence interval 0.897-0.935, p<0.0001). The best compromise between 89,8% specificity and 80% sensitivity was obtained with a cut-off value of 3.94 ng/ml for PCOS diagnosis. CONCLUSIONS: Serum AMH measurement is very valuable in diagnosis of PCOS patients. The serum AMH level in women with hyperandrogenism, or oligo-anovulation could indicate the diagnosis of PCOS when reliable ultrasonography data are not available or when typical clinical and laboratory findings do not exists. The serum AMH level is a new and useful diagnostic tool in PCOS diagnosis. This article is protected by copyright. All rights reserved.
- Acta Obstet Gynecol Scand. 2013 Aug 28. doi: 10.1111/aogs.12247. [Epub ahead of print] Elevated serum levels of anti-Müllerian hormone can be ıntroduced as a new diagnostic marker for polycystic ovary syndrome. Sahmay S, Atakul N, Aydogan B, Aydın Y, Imamoglu M, Seyisoglu H. Source Subdivision of Reproductive Endocrinology, Department of Obstetrics,Gynaecology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul. Abstract OBJECTIVE: To determine the possible role of anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) with a larger population of patients and to evaluate its role as a new diagnostic marker. DESIGN: Cross sectional study. SETTING: University hospital. POPULATIONS: A total of 570 patients, with PCOS (n=419) and without PCOS (n=151). METHODS: Serum basal hormone (AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH) levels were measured. Mean hormone levels were compared and the predictive value of serum AMH level was evaluated with the use of the receiver operating characteristic (ROC) curve analysis. RESULTS: No statistically significant differences found between PCOS patients and control groups in terms age, body mass index and TSH levels. Differences between mean serum, FSH, LH and estradiol levels and LH/FSH ratio is found to be statistically significant (p< 0.001). Mean serum AMH level was higher in PCOS patients than in controls (7.34 vs 2.24ng/mL, p<0.001). The area under the ROC curve assay yielded a satisfactory result of 0.916 (95% confidence interval 0.897-0.935, p<0.0001). The best compromise between 89,8% specificity and 80% sensitivity was obtained with a cut-off value of 3.94 ng/ml for PCOS diagnosis. CONCLUSIONS: Serum AMH measurement is very valuable in diagnosis of PCOS patients. The serum AMH level in women with hyperandrogenism, or oligo-anovulation could indicate the diagnosis of PCOS when reliable ultrasonography data are not available or when typical clinical and laboratory findings do not exists. The serum AMH level is a new and useful diagnostic tool in PCOS diagnosis. This article is protected by copyright. All rights reserved.
- Acta Obstet Gynecol Scand. 2013 Aug 28. doi: 10.1111/aogs.12247. [Epub ahead of print] Elevated serum levels of anti-Müllerian hormone can be ıntroduced as a new diagnostic marker for polycystic ovary syndrome. Sahmay S, Atakul N, Aydogan B, Aydın Y, Imamoglu M, Seyisoglu H. Source Subdivision of Reproductive Endocrinology, Department of Obstetrics,Gynaecology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul. Abstract OBJECTIVE: To determine the possible role of anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) with a larger population of patients and to evaluate its role as a new diagnostic marker. DESIGN: Cross sectional study. SETTING: University hospital. POPULATIONS: A total of 570 patients, with PCOS (n=419) and without PCOS (n=151). METHODS: Serum basal hormone (AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH) levels were measured. Mean hormone levels were compared and the predictive value of serum AMH level was evaluated with the use of the receiver operating characteristic (ROC) curve analysis. RESULTS: No statistically significant differences found between PCOS patients and control groups in terms age, body mass index and TSH levels. Differences between mean serum, FSH, LH and estradiol levels and LH/FSH ratio is found to be statistically significant (p< 0.001). Mean serum AMH level was higher in PCOS patients than in controls (7.34 vs 2.24ng/mL, p<0.001). The area under the ROC curve assay yielded a satisfactory result of 0.916 (95% confidence interval 0.897-0.935, p<0.0001). The best compromise between 89,8% specificity and 80% sensitivity was obtained with a cut-off value of 3.94 ng/ml for PCOS diagnosis. CONCLUSIONS: Serum AMH measurement is very valuable in diagnosis of PCOS patients. The serum AMH level in women with hyperandrogenism, or oligo-anovulation could indicate the diagnosis of PCOS when reliable ultrasonography data are not available or when typical clinical and laboratory findings do not exists. The serum AMH level is a new and useful diagnostic tool in PCOS diagnosis. This article is protected by copyright. All rights reserved.
- Acta Obstet Gynecol Scand. 2013 Aug 28. doi: 10.1111/aogs.12247. [Epub ahead of print] Elevated serum levels of anti-Müllerian hormone can be ıntroduced as a new diagnostic marker for polycystic ovary syndrome. Sahmay S, Atakul N, Aydogan B, Aydın Y, Imamoglu M, Seyisoglu H. Source Subdivision of Reproductive Endocrinology, Department of Obstetrics,Gynaecology, Istanbul University Cerrahpasa Faculty of Medicine, Istanbul. Abstract OBJECTIVE: To determine the possible role of anti-Müllerian hormone (AMH) in the diagnosis of polycystic ovary syndrome (PCOS) with a larger population of patients and to evaluate its role as a new diagnostic marker. DESIGN: Cross sectional study. SETTING: University hospital. POPULATIONS: A total of 570 patients, with PCOS (n=419) and without PCOS (n=151). METHODS: Serum basal hormone (AMH, follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin, and thyroid-stimulating hormone (TSH) levels were measured. Mean hormone levels were compared and the predictive value of serum AMH level was evaluated with the use of the receiver operating characteristic (ROC) curve analysis. RESULTS: No statistically significant differences found between PCOS patients and control groups in terms age, body mass index and TSH levels. Differences between mean serum, FSH, LH and estradiol levels and LH/FSH ratio is found to be statistically significant (p< 0.001). Mean serum AMH level was higher in PCOS patients than in controls (7.34 vs 2.24ng/mL, p<0.001). The area under the ROC curve assay yielded a satisfactory result of 0.916 (95% confidence interval 0.897-0.935, p<0.0001). The best compromise between 89,8% specificity and 80% sensitivity was obtained with a cut-off value of 3.94 ng/ml for PCOS diagnosis. CONCLUSIONS: Serum AMH measurement is very valuable in diagnosis of PCOS patients. The serum AMH level in women with hyperandrogenism, or oligo-anovulation could indicate the diagnosis of PCOS when reliable ultrasonography data are not available or when typical clinical and laboratory findings do not exists. The serum AMH level is a new and useful diagnostic tool in PCOS diagnosis. This article is protected by copyright. All rights reserved.
- Objective: To characterize the difference in circulating anti-Mu¨ llerian hormone (AMH) levels between the main polycystic ovary syndrome (PCOS) phenotypic groups and evaluate the role of AMH in predicting the severity of PCOS. Study design: Cross-sectional, retrospective study. A total of 251 women were divided into four groups based on the main features of PCOS, as follows: Group 1 (polycystic ovarian morphology [PCOM]+/oligoanovulation [OA]+/hyperandrogenism [HA]+), Group 2 (PCOM+/OA+/HA), Group 3 (PCOM+/OA/HA+), and Group 4 (PCOM/OA+/HA+). AMH and other hormone levels were measured in serum. The main outcome was serum AMH concentrations in the main phenotypes of PCOS. Result(s): The mean serum AMH levels were 9.50 6.1 ng/mL in Group 1; 8.02 6.2 ng/mL in Group 2; 6.12 3.6 ng/mL in Group 3; and 3.06 2.4 ng/mL in Group 4. Circulating AMH levels in Group 1 (PCOM+/ OA+/HA+) were three times higher than those in Group 4 (PCOM/OA+/HA+). Conclusions: The highest AMH levels were found in cases where all three main diagnostic criteria existed. AMH levels correlate best with PCOM. In addition, oligo-anovulation contributes to increased AMH levels. Hyperandrogenism criteria were found to have less influence on AMH levels. AMH levels seem to have a diagnostic role in determining the severity of PCOS.
- Table 3. Grouping according to presence or abscence of polycystic morphology (PCOM) and according to presence of oligo/amenorhea (cycle-length>35days). Percentages of components of hyperandrogenism according to these groups. FGS= Ferriman-Gallway Score Mann whitney U, student-t and Chi square tests(comparison of values represented as percentages). *Significantly different (p<0.001) Patients were divided into two groups according to the presence or absence of polycystic ovary morphology (PCOMþ and PCOM). AMH was significantly higher in PCOMþ group compared to PCOM group (8.15.3 ng/ml versus 3.42.4, p50.001) (Table 3). Logistic regression analysis revealed a strong relation of AMH with the PCOM when AMH values are above the mean level of our study population (odds ratio¼2.49, p50.001). Relation of Antimullerian Hormone with the clinical signs of Hyperandrogenism and Polycystic Ovary Morphology Sahmay S, Aydın Y, Atakul N, Aydogan B , Kaleli S Abstract The relation of antimullerian hormone (AMH) levels with the clinical and biochemical markers of polycystic ovary syndrome(PCOS) could be different. 463 PCOS patients evaluated in this cross-sectional study.Groups were constructed according to polycystic ovarian morphology (PCOM) and menstrual cycle-length. The relation of serum AMH with androgenic hormones , menstrual cycle-length and clinical signs of PCOS were investigated. A powerful positive relation was found between the PCOM and AMH levels ( odds ratio=2.49). There was a negative correlation between age and AMH level (p< 0.001, r[correlation coefficent]= -0.155). Positive correlations were found between LH and AMH (p<0.001, r=0.25) and also between cycle length and AMH (p<0.01, r=0.27). We found a negative week correlation between AMH and FSH (p= 0.01, r= -0.19). After controlling main androgenic hormones, AMH was found to be correlated with the Ferriman-Gallway score(p=0.03, r=0.18). There was a positive relationship between hirsutism and AMH(odds ratio=1.43) , but no correlation between AMH and other parameters of clinical hyperandrogenism like; hair-loss, acne and seborrhea were identified .The strongest relation
- Mean age of participants was 25.75.5 years (15–40), mean BMI was 25.44.5 (kg/m2) (16–39). The mean serum AMH level was 7.73.36 ng/ml (0.6–23.9). Other hormonal parameters were summarized in Table 1. There was a negative correlation between the age and the serum AMH level (p50.001, r[correlation coefficent]¼0.155). Positive correlations were found between LH and AMH (p50.001, r¼0.25) and also between cycle length and AMH (p50.01, r¼0.27). We found a negative week correlation between the AMH and FSH (p¼0.01, r¼0.19) (Table 2 and Figure 1a–c).Fig.b) Correlation between AMH and FSH, LH, Free T, Total T, 17-OHP, DHEAS Pearson correlation analysis ( * statistically significant). No correlations between AMH and androgenic hormones were identified (total T, free T, DHEA-S, 17-OH-P) (Table 2). After discarding the effects of listed androgenic hormones, the effect of BMI and LH on the FGS was measured by partial correlation analysis and a positive correlation between AMH and FGS was found (p¼0.034, r¼0.18). Relation of Antimullerian Hormone with the clinical signs of Hyperandrogenism and Polycystic Ovary Morphology Sahmay S, Aydın Y, Atakul N, Aydogan B , Kaleli S Abstract The relation of antimullerian hormone (AMH) levels with the clinical and biochemical markers of polycystic ovary syndrome(PCOS) could be different. 463 PCOS patients evaluated in this cross-sectional study.Groups were constructed according to polycystic ovarian morphology (PCOM) and menstrual cycle-length. The relation of serum AMH with androgenic hormones , menstrual cycle-length and clinical signs of PCOS were investigated. A powerful positive relation was found between the PCOM and AMH levels ( odds ratio=2.49). There was a negative correlation between age and AMH level (p< 0.001, r[correlation coefficent]= -0.155). Positive correlations were found between LH and AMH (p<0.001, r=0.25) and also between cycle length and AMH (p<0.01, r=0.27). We found a negative week correlation between AMH and FSH (p= 0.01, r= -0.19). After controlling main androgenic hormones, AMH was found to be correlated with the Ferriman-Gallway score(p=0.03, r=0.18). There was a positive relationship between hirsutism and AMH(odds ratio=1.43) , but no correlation between AMH and other parameters of clinical hyperandrogenism like; hair-loss, acne and seborrhea were identified .The strongest relation
- Objective: To characterize the difference in circulating anti-Mu¨ llerian hormone (AMH) levels between the main polycystic ovary syndrome (PCOS) phenotypic groups and evaluate the role of AMH in predicting the severity of PCOS. Study design: Cross-sectional, retrospective study. A total of 251 women were divided into four groups based on the main features of PCOS, as follows: Group 1 (polycystic ovarian morphology [PCOM]+/oligoanovulation [OA]+/hyperandrogenism [HA]+), Group 2 (PCOM+/OA+/HA), Group 3 (PCOM+/OA/HA+), and Group 4 (PCOM/OA+/HA+). AMH and other hormone levels were measured in serum. The main outcome was serum AMH concentrations in the main phenotypes of PCOS. Result(s): The mean serum AMH levels were 9.50 6.1 ng/mL in Group 1; 8.02 6.2 ng/mL in Group 2; 6.12 3.6 ng/mL in Group 3; and 3.06 2.4 ng/mL in Group 4. Circulating AMH levels in Group 1 (PCOM+/ OA+/HA+) were three times higher than those in Group 4 (PCOM/OA+/HA+). Conclusions: The highest AMH levels were found in cases where all three main diagnostic criteria existed. AMH levels correlate best with PCOM. In addition, oligo-anovulation contributes to increased AMH levels. Hyperandrogenism criteria were found to have less influence on AMH levels. AMH levels seem to have a diagnostic role in determining the severity of PCOS.
- TABLE 4. Adaptation of the previous classifications for the diagnosis of PCOS, proposing an excessive FN or serum AMH concentration as a surrogate when either oligoanovulation or HA is missing