Menstrüel Siklus PDF

Menstrüel Siklus Prof Dr Nida Bayık Nişantaşı Üniversitesi Tıp Fakültesi Menarşdan, menopoza kadar üremeye yönelik her ay tekrarlayan hormonal değişiklik ve adet kanaması ile karakterize, özellikle genital sistem olmak üzere tüm organizmayı etkileyen siklik değişikliklere m...

Menstrüel Siklus Prof Dr Nida Bayık Nişantaşı Üniversitesi Tıp Fakültesi Menarşdan, menopoza kadar üremeye yönelik her ay tekrarlayan hormonal değişiklik ve adet kanaması ile karakterize, özellikle genital sistem olmak üzere tüm organizmayı etkileyen siklik değişikliklere menstrüel siklus denir. ØSiklus süresi ® 28±7 gündür Ø21-35 günde bir mens. normal kabul edilir ØMenstruasyon süresi ® 2-3 / 7 gün ØBir siklus boyunca kaybedilen kan Ø miktarı 30 ml kadardır (20-80 ml). Menarş ® ilk menstruasyon Menopoz ® mentruasyonun kesildiği an Ø Düzenli ovulatuar sikluslar menarştan 1-2 yıl sonra başlar Ø İlk bir iki yıl anovulatuar sikluslar yüzünden menstrüel düzensizlik sıktır. Menstrüel Siklus Menstrüasyon Foliküler faz Ovulasyon Luteal faz  Menstrüel faz: Ø Siklusun ilk dört beş günüdür. Ø Bir önceki siklusta oluşmuş olan endometriumun fonksiyonel tabakası parçalanarak dökülür. Ø Aynı anda endometriumun bazal tabakasından yeni siklusla birlikte artan östrojen etkisi ile rejenerasyon başlar.  Folliküler faz: Ø Proliferasyon fazı da denir. Ø Menstrüel kanama sonrası başlayıp ovulasyona kadar devam eder. Ø Bu faz estrojenin proliferatif etkileri sonucu oluşur. Ø Bu faz tamamlandığında endometrium tabakası 5-6mm kalınlığa ulaşır.  Luteal Faz: Ø Sekresyon fazı da denir. Ø Ovulasyon ile birlikte başlar ve menstrüel kanamanın başlamasıyla son bulur. Ø Endometriyal bez yapılarında hipertrofi, görülür. Endometrium stroması ödemli bir hal alarak genişler. Ø Bu faz sonunda ortaya çıkan iskemik değişikliklerle menstrüasyon izlenir Düzenli bir menstrüel siklus için: Sağlam çalışan bir hipotalamus-hipofiz- over aksı gerekir Ayrıca sağlam bir genital trakt normal olmalıdır.  CNS SSS Hipotalamus GnRH Ön hipofiz FSH LH Over Estrogen progesteron Uterus Sağlam hipatalamo-pituiter-ovaryan aks n GnRH (portal sistem anterior pituiter) n LH, FSH n E2, progesteron n İntraoveryan otokrin / parakrin sistemler İnternal genital sistem ile bağlantılı sağlam bir eksternal sistem n Vajinal orifis n Serviks n Uterin kavite nHipotalamustan 10 aminoasitli bir dekapeptit olan GnRH pulsatil tarzda salgılanır. (2 dk) n GnRH’nın yarıömrü beş dakikadır Foliküler fazda GnRH frekansı daha hızlı Luteal fazda frekans düşük ancak amplitüd yükselir. Hipotalamus Ön Hipofiz FSH LH  FSH ØGranüloza hücrelerinde proliferasyona ve östrojen üretimine neden olur ØGranüloza hücrelerinde FSH ve LH reseptör sayısını arttırır ØLH reseptörlerinin indüksiyonu LH ØTeka hücrelerinde androjen sentezini arttırır ØGranüloza hücrelerinde yeterli LH reseptörü oluşunca ØProgesteron üretimine yol açar ØFollikülden ovumun atılmasını sağlar Øİlk foliküler gelişim hormonal etkiden bağımsız ØFSH stimulasyonu bir grup folikülün atreziye gitmesini önleyerek preantral safhaya ulaştırır ØFSH ile indüklenmiş aromatizasyon granuloza hücrelerinde östrojen üretimi sağlar ØFSH ile birlikte östrojen, granulaza hücrelerinde ØFSH reseptör sayısını artırarak granuloza hücreleinde proliferasyona neden olur. ØFSH ® foliküler büyüme ØFSH ® granüloza hücrelerinin çoğalması ØGranüloza hücreleri ® Estrojen üretimi  Kolesterol 27 C Pregnanlar Progestinler 21 C Kortikosteroidler Androstanlar Androjenler 19 C Estranlar Estrojenler 18 C  Preantral Follikül Oosit büyür Zona pellusida oluşur Granüloza katmanları artar Teka oluşmaya başlar  Preantral Follikül FSH reseptörleri ortaya çıkar FSH kendi reseptör sayısını artırır : up-regülasyon FSH aromataz aktivitesini aktive eder Androjen baskın ortamda ise 5-a redüktaz aktive olur aromatizasyon estrojenler inhibitör androjenler 5-a redüksiyon 5-a androjenler  Antral Follikül FSH ve E2 etkisi folliküler sıvı artar ve kavitasyon oluşur Teka ve granuloza hücrelerinde LH reseptörleri ortaya çıkar P450scc, 3-b OHSD aktivitesi başlar. LH, LDL kolesterolu hücre içine, mitokondriye sokar Teka hücrelerinde p450 c17 aktivitesi başlar  Teka hücrelerinde üretilen androjenler FSH’ın etkisi ile granulaza hücrelerinde aromataz enzimi ile östrojene dönüşür  İki Hücre Teorisi Granuloza hücreleri Teka hücreleri  Feed back sistem ØÜretilen östrojen hem hipofiz üzerinden FSH üretimini azaltırken, hem de hipotalamus üzerinden GnRH üzerinde azaltıcı etki gösterir ØYüksek doz östrojen LH üzerinde stimülatör etki yapar ve böylece ovulasyon öncesinde LH piki izlenir ØBaşarılı bir folikül, en yüksek aromataz seviyesi, yüksek estrojen konsantrasyonu olan foliküldür ØGeç foliküler fazda estrojen seviyeleri yavaşça ama sürekli yükselirken ovulasyondan 24-36 saat önce hızla yükselerek pik yapar. ØÖstrojenin pik yapmasıyla LH ani yükselişi görülür.  LH Surge E2 200 pg/mL üzerinde 50 saat Follikül>15 mm  Luteal faz Ø Progesteron üretimi ile karakterizedir Ø Oositin atıldığı folikül korpus luteum adını alır Ø Gebelik oluşmaz ise E2, progesteron düzeyleri hızla düşer Ø Gebelik oluşmaz ise ovulasyondan 9-11 gün sonra korpus luteum hızla regrese olur Ø Ortalama luteal faz 14 gündür, ancak foliküler fazın süresi değişir Gebelik oluşur ise KL 7. haftaya kadae progesteron salgılamaya devam eder  Endometrial Siklus Menstrüel endometrium Proliferatif faz Sekretuar faz İmplantasyon hazırlığı Endometrial kırılma – Bu değişimler “fonksiyonalis” de olur. – “Bazalis” rejenerasyon içindir.  Menstrüel endometrium Ø Endometriumun üst 2/3 bölümü her mens ile dökülen siklik hormon değişikliklerine duyarlı fonsiyonel tabakayı ve alt 1/3 kısmı ise rejenerasyonu sağlayan bazal tabakayı oluşturur. Ø Siklusun ilk 5 gününde deskuamasyon ve rejenerasyon fazları iç içedir. Endometriumun fonksiyonel tabakası bu aşamada dökülürken alttaki bazal tabakadan da rejenerasyon başlamıştır.  Proliferatif faz Ø Sonra ovulasyona kadar, proliferasyon fazı da dediğimiz, endometriumun bez ve glandüler yapılarında mitoz artışı ile karakterize dönem başlar. Ø Bu dönemde bezler boyutça büyür ve yüksek mitotik aktivite gösterirler.  Sekretuar faz Ø Ovulasyondan sonra progesteronun etkisiyle luteal fazda sekresyon fazı da denen sürece girilir. Ø Sekresyon fazında endometrium stromasında giderek artan ödem ve glikojen depolanması gözlenir. Ø Glandüler yapılar kıvrımlı ve geniş içi sekresyonla dolu hal alırlar.  İmplantasyon fazı 21-27. günlerde (postovulatuar 7-13) arasında endometrium 3 katmandır – Alt 1/3 bazalis – Orta 1/3 stratum spongiozum – Üst 1/3 stratum kompaktum 21-22 günlerde PG sentezine bağlı olarak ödem artar 22. günde endotel hücre mitozu başlar  Korpus luteumun regresyonuyla birlikte, endometrium stromasında lökosit infiltrasyonu ve ödem gözlenir. Spiral arterlerde vazokonstriksiyon olur. Oluşan doku iskemisi ve spiral arter kasılmalarıyla birlikte endometriumun üst tabakası nekroze olur ve kanla karışarak adet kanı olarak vücuttan atılır.  Endometrial kırılma fazı Trofoblastik hCG olmaksızın 25. günde luteolizis olur ve estrojen ve progesteron azalır – Vazomotor reaksiyon – Apoptozis, doku kaybı – menstruasyon  Menstruasyon Enzimatik doku yıkımı – MMP – Plazmin – Spiral arter vazokonstriksiyon Estrojene bağlı doku proliferasyon Pıhtılaşma, trombosit agregasyonu  Menstruasyon Ø 35 gün: oligomenore Ø Hipomenore 80 ml Ø Menoroji>8 gün Ø Ara kanamalar --- metroraji Ø Menometroraji  ABNORMAL UTERINE BLEEDING R. Nida Bayık, M.D., Professor Nişantaşı University, Faculty of Medicine Department of Obstetrics & Gynecology 2024  Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011; 29(5):383-90.  Fraser IS, Critchley HO, Broder M, Munro MG. The FIGO recommendations on terminologies and definitions for normal and abnormal uterine bleeding. Semin Reprod Med. 2011; 29(5):383-90.  NEW TERMS Disturbances of Regularity Irregular menstrual bleeding (IrregMB): menstrual cycle is irregular with >20 days in individual cycle lengths over a period of 1 year. Absent menstrual bleeding (amenorrhea): No bleeding in a 90-day period.  NEW TERMS Disturbances of Frequency Infrequent menstrual bleeding (oligomenorrhea): One or two episodes in a 90-day period. Frequent menstrual bleeding: More than four episodes in a 90-day period (this term only includes frequent menstruation and not erratic intermenstrual bleeding; it is very uncommon).  NEW TERMS Disturbances of Heaviness of Flow Heavy menstrual bleeding (HMB): This is the most common clinical presentation of AUB. HMB is defined as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. (National Institute for Health and Clinical Excellence. Clinical Guideline 44; Heavy menstrual bleeding.) Heavy and prolonged menstrual bleeding (HPMB): This complaint is much less common than HMB on its own. The distinction from HMB is worth making because these two symptomatic components may have different etiologies and may respond differently to therapies. Light menstrual bleeding: This is based on complaint by the patient, is only rarely related to pathology, and is usually a cultural complaint in those communities where a heavy, ‘‘red’’ bleed is valued as a perceived sign of health.  NEW TERMS Disturbances of the Duration of Flow Prolonged menstrual bleeding: Recommended to be used to describe menstrual periods that exceed 8 days in duration on a regular basis. This phenomenon is commonly associated with heavy menstrual bleeding (‘‘heavy and prolonged menstrual bleeding’’ [HPMB]). This ismuch less common than HMB of normal duration. Shortened menstrual bleeding: A very uncommon complaint and defined as menstrual bleeding of no longer than 2 days in duration. The bleeding is also usually light in volume and is uncommonly associated with serious pathology (such as intrauterine adhesions and endometrial tuberculosis).  NEW TERMS Irregular Nonmenstrual Bleeding Nonmenstrual bleeding is common and usually consists of the occasional episode of intermenstrual or postcoital bleeding associated with minor surface lesions of the genital tract, but such bleeding may herald more serious lesions such as cervical or endometrial cancer. Intermenstrual bleeding is defined as irregular episodes of bleeding, often light and short, occurring between otherwise fairly normal menstrual periods (Fig. 2). This bleeding may occasionally be prolonged or heavy, and it may occur on a regular basis around ovulation as a physiological event in 1–2% of cycles. Women with surface lesions of the genital tract may typically experience bleeding during or immediately after sexual intercourse (postcoital bleeding). The term acyclic bleeding is rarely used but encompasses those few women who present with totally erratic bleeding, with no discernable cyclic pattern, usually associated with fairly advanced cervical or endometrial cancer. Premenstrual and postmenstrual spotting (or staining) are descriptions of very light bleeding that may occur regularly for 1 days before or after the recognized menstrual period. These symptoms may be indicative of endometriosis or endometrial polyps or other structural lesions of the genital tract.  NEW TERMS Disturbances of Frequency Infrequent menstrual bleeding (oligomenorrhea): One or two episodes in a 90-day period. Frequent menstrual bleeding: More than four episodes in a 90-day period (this term only includes frequent menstruation and not erratic intermenstrual bleeding; it is very uncommon).  NEW TERMS Acute or Chronic Abnormal Uterine Bleeding It is proposed that acute AUB is ‘‘an episode of bleeding in a woman of reproductive age, who is not pregnant, that is of sufficient quantity to require immediate intervention to prevent further blood loss.’’ Chronic AUB is ‘‘bleeding from the uterine corpus that is abnormal in duration, volume, and/or frequency and has been present for the majority of the last 6 months.’’ Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders.FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011. PMID: 21345435 Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders.FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011. PMID: 21345435 Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders.FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011. PMID: 21345435 Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders.FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011. PMID: 21345435  AUB: Etiology § Trauma § Iatrogenic § Cervical laceration § Exogenous estrogen § Foreign body § Intrauterine device (IUD) § Organic § Heparin, Coumadin § Pregnancy complication § Systemic § Uterine leiomyoma § Hepatic disease § Adenomyosis § Thyroid disease § Endometrial polyp § Hyperprolactinemia § Endometrial hyperplasia § Renal failure § Malignancy (cervix, uterus) § Other § Dyscrasias § Anovulation (DUB) § Von Willebrand’s Disease § Thrombocytopenia  AUB: Evaluation § History § Detailed menstrual history (volume, duration, intervals) § Symptoms associated with ovulation § e.g. breast tenderness, bloating, mood changes § Associated symptoms § e.g. dysmenorrhea, post-coital bleeding, galactorrhea, hirsutism § Weight changes § Medical history and medications § Pelvic Exam § Cervical and vaginal lesions § Size, shape of uterus  AUB: Evaluation § Laboratory § Urine pregnancy test § CBC with platelets § Coagulation studies § Thyroid studies (TSH, T4) § Prolactin § Diagnostic Procedures § Pap smear § Endometrial biopsy (EMB) § Transvaginal ultrasound § Hysteroscopy § Saline-infusion sonography (SIS)  Diagnosis: H&P History – Menstrual bleeding hx (incl. severity and assoc pain) – FHx: AUB/ bleeding disorders – Meds: warfarin, heparin, NSAID, OCP, ginkgo, ginseng, motherwort Physical – PCOS: obesity, hirsutism, acne – Thyroid dysfunction: cold/heat intolerance, dry skin, lethargy, proptosis – DM: acanthosis nigricans – Bleeding disorder: petechiae, pallor, signs of hypovolemia – Pelvic exam  Diagnosis: Labs and Imaging Labs – Pregnancy test – CBC – Targeted screening for bleeding disorder (when indicated) – TSH – Gonorrhea/Chlamydia in high risk patients Imaging: – TVUS – Sonohysterography – Hysteroscopy – MRI Endometrial biopsy  Common Differential by Age 13-18 19-39 40-Menopause Anovulation Pregnancy Anovulatory bleeding OCP Structural Lesions Endometrial hyperplasia/ Pelvic infection (leiomyoma, polyp) carcinoma Coagulopathy Anovulatory cycles (PCOS) Endometrial atrophy Tumor OCP Leiomyoma Endometrial hyperplasia Endometrial cancer (less common) Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders.FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011. PMID: 21345435 Uterine Evaluation1  Management Medical management should be initial treatment for most patients Need for surgery is based on various factors (stability of patient, severity of bleed, contraindications to med management, underlying cause) – Type of surgery dependent on above + desire for future fertility Long term maintenance therapy after acute bleed is controlled  Management Continued Determine acute vs. chronic If acute, signs of hypovolemia/hemodynamic instability? – If yes, IV access with 1 to 2 large bore IV; prepare for transfusion and clotting factor replacement Once stable, evaluate etiology (PALM-COEIN) Determine Treatment  Medical Management Conjugated Equine Estrogen Combined OCPs Medroxyprogesterone Acetate Tranexamic Acid Long term therapy: levonorgesterel IUD, OCPs, progestin (PO or IM); unopposed estrogen should not be used long term Treatments differ for pts with bleeding disorders – Ex: desmopressin can help in vWF disease, etc – Avoid NSAIDs  Surgical Management Options D&C Endometrial Ablation Uterine Artery Embolization Hysterectomy Management of Abnormal Uterine Bleeding in Perimenopausal Women Prof Dr Nida Bayık Perimenopause — Perimenopause (around menopause) is a transition phase, begins several years before menopause. — Estrogen levels gradually decline. — Irregular menstrual periods, hot flashes, vaginal dryness, sleep disturbances, and mood swings are common, normal signs of perimenopause. Perimenopause Menstrual Cycle Anovulatory Bleeding — Corpus luteum is not produced — Ovary fails to secrete progesterone — Continuous, unopposed E stimulation of endometrium: — Endometrial proliferation without P-induced differentiation / stabilization — Endometrium becomes excessively vascular without stromal support à fragility and irregular endometrial bleeding New FIGO Nomenclature & classification of AUB Suggested “normal limits” for uterine bleeding in the mid-reproductive years Abnormal Uterine Bleeding New Terminology by FIGO uTerm HMB (Heavy mentrual bleeding) has replaced the term Menorrhagia: Bleeding that occurs at regular intervals, loss of ≥ 80 mL blood per uDUB has been replaced by BEO(Bleeding of Endometrial origin) Terminology abandoned by FIGO Munro et al. Int J Gynecol Obstet 2011; 113: 3-13 Causes of heavy menstrual bleeding ‘PALM’ ‘COEIN’ (structural (non-structural abnormalities) abnormalities) -Polyp —Coagulopathy —Adenomyosis —Ovulatory dysfunction —Leiomyoma —Endometrial —Malignancy and —Iatrogenic hyperplasia —Not yet classified ENDOMETRIAL POLYP Adenomyosis TVS Adenomyosis Fibroid Uterus Submucous Fibroid Invasive cervical cancer Carcinoma endometrium PCOS Anovulatory Bleeding: Later Reproductive Age (40-Menopause) — Incidence of anovulatory bleeding increases due to declining ovarian function. — Incidence of endometrial CA in women 40-49 years: 36.2/100,000 — All women >40 yrs who present with suspected anovulatory bleeding merit endometrial bipsy. Each case has 1 identified abnormality >1 positive category Diagnosis of Abnormal uterine bleeding — Medical history — Physical examination — Laboratory tests — Imaging tests AUB-History Age of onset of menses Frequency/duration of menses Quantity of flow,number of pads,passage of clots and flooding — Intermenstrual bleeding — Postcoital bleeding — Dyspyerunia — Use of contraceptives/medication — Family history of menarche, menopause,malignancy AUB-History — Pelvic Pain — Postcoital pain — Vaginal Discharge — Excessive bruising/bleeding from other sites — History of post partum haemorrhage — Family history of bleeding problems — Urinary symptoms — Weight change ,heat or cold intolerance Stress Physical examination General examination Abdominal examination Vaginal / per speculum and pelvic examinations Examination GPE Assess for obesity, hirsutism, stigmata of thyroid disease (hypothyroidism associated with anovulation), signs of hyperprolactinemia (visual field testing, galactorrhea) ABDOMINAL EXAMINATION Abdominal masses Laboratory and Imaging Tests — CBC,Coagulation screen — Assays for thyroid hormone — HVS,endocervical swab,Pap smear — Pelvic ultrasound — Abdominal/Transvaginal Ultrasonography (TVS) — Sonohysterography,saline infusion — Endometrial biopsy — Endometrial sampling by Pipelle — Hysteroscopy — Dilation and Curettage (D&C) Biopsy should be performed as first line test(ACOG) — Aged >45 years — Irregular or intermenstrual bleeding CT scan and MRI(special circumstances)) Transvaginal ultrasound Saline infused sonohysterography Sonohysterogram Hysteroscopy Evaluating endometrial cavity Hysteroscopy “Gold standard” for endometrial assessment Office procedure Thorough, direct inspection of endometrial cavity Directed biopsy or treatment possible (e.g., polyp excision) Drugs for HMB — NSAID’s — Tranexamic acid — COCP’s — YAZZ — Diane-35 — GİNERA — Climen-cyloprogynova — Oral Progestogens — Mirena — Danazol/GNRH analoges Cyloproginova Climen Composition Composed of estradiol-17 valerate and cyproterone acetate * Presented in calendar packs of 21 tablets each * First 11 tablets contain estrogen only; the other 10 contain both hormones Contraindications of HRT — PREVIOUS THROMBOEMBOLIC DISEASE — IMPAIRED LFT/ LIVER DISEASE — CARCINOMA BREAST — CARCINOMA ENDOMETRIUM — FIBROIDS &ENDOMETRIOSIS(relative) HYPERTENTION,DIABETES,CARDIO- VASCULAR DISEASE ARE NOT C/I Oral Progestogens — Norethisterone acetate(Primolute N) — Dose is 5-10mg three times a day from day 6 to 26 of the cycle The levonogestrel intrauterine system (LNG-IUS), Mirena What is Mirena® used for? Indications: —Contraception —Treatment of heavy menstrual bleeding (idiopathic menorrhagia) —Protection from endometrial hyperplasia during oestrogen replacement therapy Endometrial effects with Mirena® Before Mirena® After Mirena® Endometrial changes Menstruation Ovulation Reduced Ovulation menstruation Surgical treatment Endometrial ablation —First-generation: — Rollerball — Transcervical resection of the endometrium —Second-generation: — Impedance-controlled bipolar radiofrequency — Balloon thermal — Microwave — Free-fluid thermal Surgical treatment — Uterine artery embolization(UAE) — Hysteroscopic myomectomy — Myomectomy — Hysterectomy — Abdominal — Vaginal — Laparoscopic Uterine artery embolization for Fibroids