Up to date Gynecology (Volume 1) By Staff members of Obstetrics and Gynecology Department Ain Shams University Seventh Edition (reprinted 2017) Chief Editor Prof. Sherif A Akl Heal of Obtr and Gynecology Deperinen reso of Obsce anl Concer “in Shona Uatereiy Updated and Reviewed by Prof. Ayman Abulnour Profesor of Obrrs and Gneolegy iin Shans Unies Editor Dr. Mohamed El-Mandooh Lecturer of Obstertes and Gynecology Ain Shams Universitylst Edition 2001, (Chief Editor: (e Prof. Hamdi El-Kabarity Conkaito ‘Late Prof. Sameh Abdel-Hafer ccond Ralition 2003, Chiet Eattor: Prot. Aly Ryan Cokaitors: Prot. Mohamed Nabogh El-Mahallawi Prof. Essam Ammar hird Ealtion 2005, (Chief Bator: "ol. Mahmoud EL-Shourbagy Connaito ‘Prof. Mohamed Nabegh El-Mahallawi Prof. Amr Nadim ourth Ration 2006 ‘Chief Editor: Prof. Mahmoud EL-Shourbagy Coaitors: Prof. Mohamed Nabegh El-Maallawi Prof. Amr Nadim (th Fdition 2007 (Chit Balto: Prof. Mohamed Nabegh El-Mahallawi CoRaiter: Prof. Ame Nadim evsed Fifth Eaton 2009 ‘Chief Editor: Prot. Mohamed Nabegh El-Mahallawt Co-editor Prof. Ame Nadim uth Baition 2012 (Chief Ealtor: Prof. Ahmed I. Abou Gabal CoBaitor: Prof. Mohammad Abd Ehameed venth Edition 2015 ‘Chief Faltor: Prof. Ala ENGhannam Co-kattor Prof, Ayman Abulnour Dr. Mohamed Abd El Aleem Copyright reprinted 2017 by Obstetrics and Gynecology department Ain Shams University I rights reserved. No part ofthis book may be used or reproduced in any manner whatsoever thout written permission, except in the case of brief quotations embodied in critical articles or publishers have male every effort to trace the copyright holders for borrowed material. IF y have inadvertently overlooked any, they will be pleased to make the necessary angements atthe fist opportunity. th Ealtion (reprinted 2017) elcome all suggestions, For any suggestions please submit to Obstetrics and Gynecology DepartmentAcknowledgements like to express my thanks and appreciation to the whole staff members of Obstetrics and Gynecology Department for the tremendous effort that has been spent to accomplish this work with special thanks to: (Alphabetically) Dr Ahmed Abd El Shafy Dr Ahmed El Anwar Dr Ahmed Kotb Dr Kamal El Deswky Dr Mohame Hamed Dr Mohamed Faris Dr Mortada El Saied Dr Radwa Mansour Dr Rasha Medhat Dr Walied Khalaf Prof. Sherif A Akl ai of Obras and Geog Depronet ‘ress of Oster an Comey “Ain Shams UniversiPreface of the seventh edition (reprinted) Dear students and staff Extending to the invaluable and endless effort of the staff members of our department in accomplishment of this task of editing, revising and following the publishing of this book in its consequent editions and reprints, I would like to emphasize that science is almost changing and we try to update our scientific material and training to cope with the practice status quo. Actually our aim is to sustain highly qualified graduates who will add much service and benefit to the community and science. Prof. Sherif A Aki Head of Obstetrics and Gynecology Department Profesor of Obsteics and Gynecology ‘dn Shams University Preface of the seventh edition Dear medical students, ‘Writing a book for medical students is no easy task. The feat becomes so much harder if a rapidly evolving clinical science is the subject. In preparing the fifth edition of the Obstetrics and Gynecology book for our department, the editorial team concentrated on updating knowledge as well as removing and modifying areas of the science which are no longer considered valuable or important. The aim of the core curriculum is to reach the accredited undergraduate program in Egypt. This book offers the reader a comprehensive review of knowledge, No literary work can claim perfection; in that spirit the authors encourage any constructive suggestions for further editions. This book represents the collective efforts of the whole members of Obstetrics and Gynecology Department, Ain Shams University. Prof. Alaa El Ghannam Head of Obuetrcs and Gynecology Department Profesor of Obstetrics and Gynecology ‘din Shams UniversiTitle Page Chapter 1 (Basic science) Anatomy 1 Embryology 7 Physiology 26 Chapter 2 Puberty 37 ‘Menopause 41 ‘Chapters (Amenorrhea) Etiology a7 Assessment I 33 Management 56 Chapter 4 (Anovulatory disorders) Introduction 58 Polycystic ovary 60 Hyperprolactinemia 6 Hyperandrogenism 65 Other disorders Gl Chapter 5 (menstrual disorders) Abnormal genital bleeding I 70 Assessment of bleeding 4 Dysmenorrhea 17 Chapter 6 (Inferti tiology_ _ 82 85 Management. 5 Chapter 7 (family-planning) Introduction 99 Physiological methods 101 chanical methods 102 Intrauterine device 103 Hormonal contraception 107 Surgical sterilization 113Basic — ScienceeT applied Anatomy Ed ns Pubis (mons veneris) Pad of fat covering symphysis pubis + Actas cushion duting intercourse, In female; the hair is straight at upper border of mons pubis. + While in male; the apex may reach umbilicus 2: Labia 3-Labia minora: | Two elipical folds of skin raised By | Two folds of non-keratinized skin a to labia majora (thin & redundant) “Anteriorly divi into the underiying fat. | Anterior arse fom | Post: wat tom peter commisira | Skin is covered by hair & contains many | sebaceous & sweats (apocrine) glands. | folicies. Occasionally they contain canal of | = secretions with characteristic odour Nuck (a fold of peritoneum) | Homologue to male scrotum. Homologue to flor of penile urethra. 4. Glitoris + Length < 2-3 em long. It ies 2-3 em above uretra + Form very sensitive (ich nerve supply) & erectile (2 corpora cavernosa) Parls remnants are called: caraunculae myrtiformes 9- Bartholin glands (greater vestibular) Site: - One on either side ofthe vagina ~ Embedded in the posterior lower % ofthe vestibular bulb + Structuy = Size ofa pea (normally can't be felt except i infected) = Compound racemose glands Duct is 2~3 am long & opens on either side of introitus (5, 7 o'clock) ‘+ Function: alkaline vaginal secretion for lubrication during intercourse Bl m ‘Internal pudendal artery (mainly) + Femoral a. (superficial & deep external pudendal) # Nerve supply ‘+ Pudendal nerve (motor & sensory) + Sensory supply also from: 1. Perineal branch of lateral & posterior cutaneous nerve of thigh 2 ilioinguinal, tlohypogastiic 3, Genital branch of genitofemoral nerve 3 Lymphaties ean wa Inguinal & femoral LN ‘ho ‘The gland of Cloquet in eae the femoral canal J [External iliae LN - sescul 7] “ arene Rouna fe, | eM Common itiae LN | | iam + Paraaortie LN‘Superficial inguinal lymph nodes Deep inguinal iymph nodes i,‘© Elastic fibromuscular canal extending from vulva to uterus ‘The ontice is partially closed by hymen in virgins ‘Cervix protrudes through the upper part of anterior wall making 4 fornices Anterior shallow... Posterior deep,......2 lateral fomnices ‘© Thorefore the anterior wall is 8 em vile posterior walls 10 em » Relations ‘* Anteriorly < lower %: (urethra)......upper %: (bladder) ‘+ Posteriorlyse (lower Ys: perineal body)...(mid %: rectum)..(upper %: D.pouch) = Laterally = ‘©. Lateral fornix is related to ureter which passes 1% cm above and lateral tot. ‘© Lateral vaginal wall related to + Cardinal ligament (and other pelvic cellular tissue) + Levator ani muscie (and urogenital diaphragm) + Vestibular bulb (with Bulbo-spongiosus muscle) ~ Bartholin gland > watt ‘+ Two walls (anterior + posterior) opposed to each other (potential space) transverse section. .<2...tH-shaped longitudinal section. =>..Flask shaped + Muscle: 2 layers (outer longitudinal, inner cular) + Epithelium (mucosa, vaginal skin) 4] Stratified squamous epithelium non-keratnized 2] Thrown into folds (rugae that allow distensibility) 3] No glands (secretions come from the @cervx, vaginal transudaton; ‘secretions from eBarthoin glands) 4] Estrogen increases thickness & glycogen deposition. Doderein baci {acts on this glycogen by anaerobic metabolism —» pH 3.5-4.5 ‘hich Is the man protective mechanism against infections (hus ‘vulvovaginitis may occur pe-pubertal or post-menopausal) > Blood supply.....very rich.. '. Vaginal artery (rom internal iliac artery) is the main blood supply to the upper vagina . Additional branches to the lower vagina fror = Middle rectal artery (rom internal iliac artery) = Inferior rectal artery (rom the internal pudendal artery) «. Uterine artery branches + Circular artery of cervix -> anterior & posterior azygous arteries + Descending cervical artery (cervicovaginal artery) > Nerve sumply <> upper part (insensitve)......lOWer Yé: pudendal nerve > Lymphatics <> upper part drain with cervix.....Jower Y drain with vulva > Vaginal support <> attachment to corvx:@ cervical ligaments; @ levator ani ‘©direction ofthe vaginal axis backwards i?Hollow pear shaped muscular organ Dimensions = 3 x2 x1 Inches but (3% x 2% x 1% in mult-gravida) Weight = 50.gm but (70-80 gm in mutt-gravida) itis formed of 3 parts: the body, cervix and isthmus Parts 1- Body (corpus uteri) It consttutes the upper % ofthe uterus (2 inches) + dungion wth tubes i erm, part above insertion of tubes Is tandue ~ Antefior:uterovesical pouch (between bladder & uterus) = Posterior: Douglas pouch (between rectum & uterus) ‘% Mvometzium (3 layers) = Outer longitudinal = Inner circular + Middle oblique (makes 8 shaped figures around vessels) ‘ Endometrium “= Columnar epithelium (partially ciliated) = Glands (simple tubular), stroma & blood vessels. = Sensitive to cyclic hormonal changes (endometrial cycle) 2- The cervix ' occupies the lower third (1 inch) + thas a spindle shaped canal communicated with = The uterine cavity above by internal 0s (diameter is 3-4 mm) = The vagina below by the external os (rounded in nulipara & slt-shaped in the multipara). External os is at the level of ischial spines. “+ The cervix is divided into 2 parts by the attachment of the vagina. The ‘supravaginal portion and the porto vaginal ‘+ Histologically: = The cervical canal (endocervix) is lined by tall columnar partially ciliated Ccolls with basal nuclei & interrupted by low basal cuboidal cals. ~ The portiowvaginalis (eclocorvix) is covered by stratified squamous epith &- Isthmus ‘= 3-5 1mm (covered by loose peritoneum) + Between Anatomical intemal os (between body & cervix) above and Histological internal os below (between endometrium & endocervix) + In pregnancy forms —» the lower uterine segment (10cm) Se a nail ee ee at ae ie “Membranes Firmly adherent Loosely adherent a ea Leon & retracts) | (dilates & stretche S77.#3 Blood supply of uterus O uterine artery branch from intomal iliac artery (anterior division) @ ovarian artery.,...-..braneh from aorta (at level of L.2) # Relation bet. body & ex Corpus | Goi Intrauterine fife 3 infantile Propuberial Alt Wenop: {2 Nerve supply ‘1-Sympathetic 17 —> 2 Post-ganglonicflbers pass in the (superior hypogastric plexus) over the promontory of sacrum & divides into @ right & let presacral nerves (on both Sides ofthe rectum) 2. Parasympathetie S 2,9, 4 Praganglioni fibers (@ Pelvic / Splanchnic) pass along with the pudendal nerves» relay at ganglia in or near wall of viscera The pave planus (inferior hypogaste plexus) ‘The cers only Sensitive to dilatation “The body is oaly sensitive to distension perineum, lower % vagina =» allsomatic | # Lymphatic drainage of the uterus: *+ Of the cervix and the lower third of uterine body: 4. Paracervical LN al crossing of ureter of the uterine artery. 2. Extema iliac LN around extemal iliac vessels. 3, Internal liac LN around internal iliac vessels. 4. Obturator LN near obturator foramen. 5. Sacral LN upon the sarum. + Of the middie third of the uterine body: ‘To the internal iliac LN directly + Of the upper third of the uterine body: “To the paraortc LN with the ovarian vessels + Comu of the uterus ‘Nay drain through the round ligament tothe superficial inguinal LN # Normal position of the genital system ~r Ante-Version => whole uterus is inclined forward on vaginal axis by 90° ‘due fo tension between uterosacral & round ligament + Ante-Flexion <> the body is bent forwards on the cervix by 160-170 ‘due tothe fone of the uterine muscles 20 % of females the uterus may be Normally etroverted -> RVF ‘Sr Extornal 0 lies normally at/ above the level ofthe ischial spines ‘Vagina is directed upwards & backwards forming 45.60° with horizon ia $f Supports of the uter ‘AVE position Uterine Ligaments (true only) LLevator Ani muscle Peritoneal attachment Position of the surrounding viscera # Uterine ligaments 1- Corporal (false) ‘AJ Broad ligament “+ Fold of peritoneum betwaen lateral ulerine border & lateral pelvic wall © Contents 1. Parametiium (loose connective tissue continuous with the ‘extraperitoneal tissue of the pelvis). 2. Upper border: (medially; the Fallopian tube runs, laterally; the Infundibulopetvic ligament) 3. Uterine & ovarian vessels 4. Vestigial remnants (epoophron, paroophron, Gartner duct) £8] Round ligament * Rises from uterine cornu through inguinal canal to insert in labia majora + Raises a ridge on the anterior (inferior) layer of broad ligament + Important to maintain anteversion + Supplied by Sampson artery (rom ovarian artery) & another branch from Inferior epigastic artery ] Ovarian ligament > from uterine comu to ovary 2+ Corvical (true) ‘AJ Anteriorly = Pubo-cervical lig. (pubo-cervico-vesical fascia) '* Extends to the posterior surface ofthe pubis surrounding the urethra + Distension of urinary bladder prevents good formation of this ligament B] Laterally =» Mackenrodt lig. cardinal lig transverse cervical lig. “= Strong, fan shaped ligament “ From lateral part of cervix & upper part of vagina {o lateral pelvic wal (white ine) ‘The ureter passes through it (in the ureteric canal) ‘IU forms the base of the broad ligament C] Posteriorty w+ Uterosacral ligament + From back of cervix to middle sacral piece (S2,3) + Formed of 2 pairs (surrounds the rectum) the only tre ligament (others are condensed connective tissue, smooth muscle, elastic fibers) a eeeres Fallin ovary tube - Latham son ‘womgiptnm bso Uterus, cervixand isthmus __|__Antero-verted flexed uterus Ovarian Ligamen sgt Posterior view of the uterus —] 1. usta se Ute -0 2a rane vagal ‘al 2: Te tae seus ‘crsToREcTOCELE ‘The vaginal sulot Lateral relations of the vaginaTT > shape * Length about 10 om (4 inch) Extends from the cornu to open atthe infundibulum * Present in the upper free border ofthe broad ligament * The mesosalpinx is part of the broad ligament between the tube and the ovary * Largest fimbri Is called fimbria ovarica:- important for ovum pick-up © The utero-tubal sphincter Is found at the tubal ostia that prevents retrograde, menstruation ino the pelvis > Layers = Pefitoneal coat + complete except the interstitial part & the flaor = Muscle —> inner circular & outer longitudinal = Endosalpinx > thrown info folds. Cells are columnar partially ciliated, partially ‘secretory peg cells (Immature or reserve cells) > Blood supply <> both the uterine & ovarian vessels > Position Lies in the fossa ovarica (a depression inthe lateral pelvic wall) ‘The ureter & inlomal iliac artery are passing longitudinally behind it * Connected to back of broad ligament by mesovarium * Connected to uterus by ovarian ligament * Connected to pelvic side wall by infundibulopelvic ligament > Size almond shaped —> 8x2 tem (S.am) > Structure ‘= Hilum -> vessels, Iymphatics, nerves enter & leave through it * Modilla > vascuiar connective tissue stroma + Cortex» flies, corpus luteum & albicans (the main compartment) » = The ovary is surrinded by tunica albuginea, which is a dense condensation of ‘the stroma covered by a single layer of cubical calls (the germinal fpithelium), that is continuous with the peritoneal surface at the * Ovary is Not covered by peritoneum ‘to allow ovulation’ » Blood supply <> ovarian artery > Lymph drainage = paraortic LN $5LL Back of the uterus Parts of Fallopian tubeeee > Internal iliac artery i _Anterior division tne ‘osumbar |__* Superior vesical (obliterated umbilical) | * Inferior vesical (vaginal) | 2Lateral sacral |__* Middle rectal (hemorroidal) 2. Muscular branch (obturator) 3-Superior gluteal [3Torminal branches (inf gluteal, int pudendal) NB - Superior rectal artery >is the continuation of inferior mesenteric artery + Inferior rectal artery <2 isa branch of intemal pudendal artory > Ulorine artery “The main vessel, a branch from the anterior division of internal iliac artery They are tortuous (o allow uterine expansion during pregnancy) * Itruns medially to cross above the lower end of the ureter lateral to the ‘supravaginal part of the cervix Then it tums upwards at the lateral border of the uterus within the leaflet ofthe broad ligament, + Branches + Tothe ureter + Circular branch —* tothe cervix + Descending branch —* to the vagina (corvico-vaginal) + Ascending branch —» gives arcuate (coronary) arteries, thus the midline of the uterus is the least vascular Radial arcuate arteries to perforate the endometrium. They will “finally divide to |- Basal artery... supplies basal parts only {2 Spiral artery...supplies the more superficial parts + Finally, it anastomoses with branches of ovarian artery atthe cornu > Ovarian artery = Aises from aorta at L2_(ust below the renal artery) Atte pelvic brim, it crosses the external liac vessels & enters the pelvis In the infundibulo-pelvic ligament + Then they pass below the Fallopian tube & curves to reach the ‘mesovarium and enter the ovary through the hilum Left ovarian vein —» drains into the left renal vein" ioe eine eae ae eee“The pelve floor consttulas the soft structures, which fl the bony outlet | of the pelvic cavily. It includes all structures between the perineal skin ‘and the pelvic peritoneum. The pelvic floor is divided by the pelvic Its divided into 2 parts * Parietal fascia ~ covers the muscles of pelvis * Visceral fasca ~» endopelvic fascia, pelvic cellular CT > This fascia forms certain strong condensations * Around the cervix = the 3 cervical ligaments * Around the uterus = parametsium (within the broad ligament) * Around the vagina = paracolpos * Between the vagina & rectum = rectovaginal fascia (2) Pelvic diaphragm > A fibromuseular sheet which supports pelvic contents > Itextende as a diamond shape from the lower border of symphysis, pubis to the 2 ischial tuberosites til the tip of cocoyx It is composed of (2 levator ani & 2 coccygeal muscles) & their supporting fascia (superior & inferior pelvic fascia) > Itis divided into 2 tangles = Anteriorly:: The urogenital tangle (diaphragm) = Posteriorly:- The anal triangle — Levator ani The right & the left muscle form a broad muscular sheet that pass downward, backward & inward, tt is perforated by the urethra, vagina and anal canal. It is composed of three parts 0 Pul * Origin: From back of S. pubis & anterior part of white line (@ thickening in the obturator fascia) * Insertion: ~ Side walls of urethra -> Pubourethralis * Side walls of vagina -» Pubovaginalis (fers of Lushka) = Side walls of rectum -> Puborectalis Tip of coceyx & anacoceygeal raphe -> Pubococeygeus proper © Iiococeygeus From white line to perineal body, anococcygeal raphe & coccyx © Ischlococeysfeus From ischial spine to coccyx & sacrum )P--ecARRRR) Sy Nerve supply. = Pudendal nerve S: 2,3,4 > perineal surface (covered by int. pelvic fascia) ~ Branches of $:3,4 roots -> pelvic surface (covered by sup. pelvic fascia) Function ~ Support of pelvic viscera > Maintain intrabdominal pressure > Sphincter to urethra, vagina & rectum {Important role in labor (rotation) [4] Perineum... 2- 5m > The area extending between skin (below) & the pelvic diaphragm (above) > Divided into 2 pouches (superficial & deep) separated by a perineal momb + Porineal muscles ~ Ar Deep Perineal Muscle 1. Deep transverse perinee! muscle 2, Sphincter urethral muscle: surrounds the urethra, - B- Superficial Perineal Muscles (muscles ofthe Vulva) 1 2, lschio-cavernosus muscle: From ischial tuberosity to be inserted around the citoris athe ischiopuiic bone, 3, Bulbo-spongiosus muscle: ‘Attached anteriorly to the sides ofthe clitoris and unites, posterioly behind the vaginal orifice and got attached to the perineal body. It diminishes the vaginal orifice at colts. + Perineal body ~ Lies between vagina & anal canal + Fibromuscular pyramidal condensation of 9 muscles 1. Two bulbo-spongiosus muscles. 2. Two superficial and two deep transverse perineal muscies. 3. External anal sphincter 4. The pubovaginalis parts ofthe two levator ani muscles. + lechiorectal fossa = Wedge shaped space on either side of anal canal filed by fat = Boundaries, + Superior & medially > levator ani + Laterally > obturator muscle and fascia = Inferiony -» skin ‘The Pudendal (Alcock’s) canal = Itis a tunnel formed by spitting ofthe obturator fossa, = It runs antero-medially from the ischial spine to the posterior ‘edge of the urogenital diaphragm. ~ ltcontains the pudendal vessels and nerve. SeLUAG CREST Pewic DAPHRAGH Pawo sai ISOM. VBEROSITY (pemeau) PEDIC CAMTY _ superficial perineal compartment _| The superficial perineal muscles _| |__thetetrssimuncies —_|__tropshtodactrsm Sea © The femoral LN (longitudinal) ~ Superficial....along the saphenous vein ~ Doop....along the femoral vein (esp. LN of Cloquet: in femoral canal) © The inguinal LN (transverse) ~ Superficial....below & parallel to the inguinal ligament = Deop....present inthe inguinal canal © The cervical LN: Paracervical + Parametrial + Uroterie + Presacral © The iliac IN ~ Internal iliac. along intemal liac vessels = Exctornal lac... Anterior, Medial, Latoral groups = Obturator (inteiliac).....near the obturator foramen = Common iliac. along the common iliac vessels © The paraortic IN > Course (10 — 18cm) = Tho ureter enters the pelvis ‘artery. It then passes downwards infront the intemal iliac vessels 10 ‘become medial to them & behind the infundlbulopelvic ligament & ovary ~ Just above the level ofthe ischial spine. it curves medially & forwards to pass through the urateric canal (In the Mackenrodt igament) tl it reaches the bladder tigone. Its crossed by the uterine artery at the base of the broad ligament. Here the ureter ie 2 em lateral fo corvix & 2 em above vaginal vault > Liable to be iu 4, Hysterectomy (abdominal or vaginal) 2. Pelvic lymphadenectomy . 3. Bilateral intemal fac artery Higation - 4. Adenexeciomy (removal of ovarian swellings) | Injury is increased in . | + Congenital malformations of he geil or urinary tract * Distorted course (cervical fibroid, broad ligamentary swelling) | ‘Extensive adhesions (endometriosis, PID, tuberculosis, spreading malignancy) | Rapid bind clamping to stop massive bleeding > To_avoid injury, we must do = Pre-operative =» IVP (intravenous pyelography) “intraoperative 1. Proper denifcatton of fe anatomical course “2, clamping mist only be done under vision 5. Clamping must be noar othe uterus 4. Insertion of ureteric catheters > Tynes of ~ Direct —> cutting, crushing, suturing «Indirect > devascularization as in radical hysterectomy ! post-radiation"FGM" is a new nomination for femelle circumcision. FGM includes various types of procedures to remove variable parts of the normal structure ofthe extemal genitalia, FGM is defined by the World Health Organization (WHO) to include all procedures that involve partial or total removal of the female extemal Qenitalia for cultural nontherapeutic traditional reasons. + Classification > Type ke Excision of the prepuce, with or without excision of part or the entire clitoris > Type: ‘APE TExcsion ofthe prepuce and clitoris, wth partial or total excision of the labia minora, > Tye ik: = Excision of part or all of the external genitalia and jeciognancving fe vaginal apeing Geftnaton = Sudanese > Tite TS or uncatsed procedures: 0g. picking, paring, seraping, {attoo, burning by cauterization andlor introduction of corrosives oF herbs into the vagina. # History & Geographical Distribution ~ FGM isa tadilonal practice and deeply roted in certain communities The history of FGM fs not very clear, however documented data showed that i is known wo be encouraged since before the Holy religions and by diferent cultures = Study of the geographical distribution of FGM among the whole world Towadays, concludes that the vast majorly of the FGM Is cared Out in middle of Aca wth Sudan and Egypt othe north = Egypt and Sudan are the only Arab counties where itis praciiced to a significant extent. = The WHO ‘ie commited to’ the aboton of all forms of FGM. It strongly condemns the Involvement of health professionals (medicalzaton OF FGM) many setng of this practice # Complications of FGM 7, Severe pain and neurogonic shock 2. Bleeding and hemorrhagic shock. 3. Damage to the urethra and vagina, 4. Infection. 85. Psychological trauma. 7. Urinary tract infections. 2. Scar and keloid formation. 8. Bartholin cysts and abscoss. 4. Implantation dermoid cyst and neuroma, 5. Senial problems: e.9. dyspareunia, “vaginismus, chronic pelvic congestion,Embryology BE # Gonadal differentiation ‘* Gonalic sex is determined at the moment of conception by the presence or ‘absence of a Y chromosome. At the sixth week of fetal life, gonads are ‘capable of differentiating into either testis or ovary. In the absence of Y- Chromosome, the gonad develops. into an ovary, even if only one X- ‘chromosome (and no Y-chromosome) is present (as in Tuner syndrome). + Tho primitive germ cells (primordial cells) appear in the wall of yolk sac (near the hindgut). These colls migrate along dorsal mesentery to reach the genital rilge (which isthe medial thickened part of the urogenital ridge) + Gorm calls will markedly increase in number by mitosis to reach a maximum of 6 7 million at the twentieth woek of gostation. Then mitosis stops and the ogonia will start the first reduction division (meiosis) in which they will be arrested in prophase (diplotene stage). ‘= An outgrowth from the surface epithelium into the substance of the ovary will form the sax cords, whila some cells from the mesenchyme will form the sex. stroma The sex cords envelop the germ calls to form the granulosa cal Primary oocytes not surrounded by these sex cord cells will (what occur in Turner syndrome). - The'sex stromawil form the theca cells (as an outer layer) #8 at bit * A large number of try folcles will be lost in intrauterine life by a process of apoptosis (programmed coll death). Thus, folicies are reduced to 1 milion at bith then atresia occurs following bith throughout life and the number is further | 16 300.000 at puberty After puberty ‘= A certain number of primordial follicles (400-1000) in each cycle will resume meiosis. Only 1 will become fully mature the dominant folicie) = 2ry oocyte + 1st polar body, while the remainder will undergo atresia. Upon fertilization, the second meiotic division (totic like) wil occur =» mature oocyte-+a 2nd polar body ‘of Ovarian folds: The ovary raises two folds: =. The upper fold forms the infundibulo-pelvic ligament . The lower fold fogms the “gubemaculum’ (a fibromuscular band) attaching the lower pole of the ovary to the inguinal region. The upper pole of the ‘gubernaculum (between the ovary & uterus) becomes the ovarian ligament, while the lower part (between the uterus & inguinal region) becomes. the round ligament, # Migration (descent) of ovaries "Descent of the ovary info pelvis Is due to unequal body growth (unk more than the rest ofthe body) & not hormone dependent (unlike the tostis) rySe "The Wolffian duct (mesonophric duct) develops under the effect of SRY = Sex determining Region of ¥ chromosome). This will direct testosterone production from the Leydig c +. The Mullerian duct (para-mesonephric dct) regross under the effect of MIF (Muerian inbtory factor) = Al (ant-Mullerian hormone) Which is produced ttom the Sorel cells in testis ‘= Vestigial romnants may be found between the 2 layers of broad ligament & may lead to the formation of large cysts later on in life (called the paraovarian oF the broad ligamentary cysts) 1. Koblet tubules =» atthe outer part of broad ligament 2. Hydatid of Morgagni ~ near the tubal fmbria 3. Epoophron = between the ovary & tube 4. Paroophron = between the ovary & uterus 5. Gartner duct ~» runs medially below the tube then passes lateral to the uterus, cervix and the vagina. In the vagina, they pass through the anterior wall and ending at the clitoris (later on they may form the Gartner cysts) # in Females + Indifferent stage: “The Mullerian duct develops in the lateral part of the urogenital Fidge as a longitudinal invagination ofthe coelomic epithelium = Controt = Due to the absence of the Y chromosome and hence the tests: 1. Mullerian ducts persists due to absence of ANH 2, Wolfian’ ducts disappears due to absence of testosterone Production (except a part called the ureteric bud) | This means that ity ieutral state during sex differentiation ‘And masculinity is the superimposed character due to presence of a Y ‘ome i = Further development ~ Mullorian duct passes downwards & curves medially to fuse with the ‘opposite duct in th midline, Then, absorption of the intervening septum will occur from below upwards he horizontal unfused parts will form ~» the fallopian tube The longitudinal fused parts form = the uterus, cervix, upper 3/4 of the vagina = The lower end of Mullerian duct will project as a tubercle into the Urogenital sinus o form a solid vaginal plate = Canalization of this plate by the sino-vaginal bulbs (at 20 weeks) will form = lower 1/4 of the vagina = The Junction between the Mullerian duct & urogenital sinus will form "= the hymen, nSa #At outer surface of urogenital sinus: 5 mesodermal swellings appear: . 4, The genital tubercle (phallus) ~ clliorls 2. The two urogenital folds = labia minora 3, The two genital (lablo-scrotal) swolings —* labia majora #8 Controt = In males: Testosterone (produced by the Leydig cells) will be transformed to the more potent diiydro-estosterone ~DHT- (by 5a reductase of prostate). This leads to enlargement of the genital tubercle to Penis & fusion ofthe genital swellings to form the scrotum. ~ In females! absence of testosterone —» feminization characters #2 Gloaca ‘The uro-rectal septum wil divide the cloaca (at 5-6 weeks) into 1. Two compartments: rectum & urogenital sinus 2 Two membranes: anal & urogenital membranes = The outmost part ofthe urogenital sinus forms >the vestibule Gonad ee Infundibulopelvic ligament Gubernacultum Genital rhage Ovarian ligament, Round lig, egress by MIF vestigial remnants *Ureteric bud Uretore buds & tigone |(mesonephric) [Cloaca: = Urogenital |). Lower 14 of the vagina | . Prostatic utercle Sinus Hymen & Vestibule Seminal colliculus Bartholin glands «Cowper's glands (Greater vestibular glands) (bulbo-urethal) Urethra, paraurethral glands . Urethra & prostate Bladder “Bladder yanus anus = Anal can Ext. gota {Genta bere | - clots | -penie Penile urethra (ventral)© External genitalia > Ambiguous genitalia (Intersex). The commonest cause is congenital adrenal hyperplasia (50% of cases) > Clitoris .Bifd clitoris (may be associated with actopia vesical) Hypertrophy (cittomegaly) -isolated or part of generalized virlization- > Labial hypertrophy which may lead to dysparvenia or disfigurement Congenital labial adhosions (however acquired adhesions are commoner due te Infection or post-menopausal atrophy and treatod by ‘surgieal separation local estrogen > Vestibular anus (abnormal insertion of the anus) © Ovaries > Aplasia& hypoplas = Complaint: primary amenorthea, infertility * Diagnosis: see amenorrhea Treatment: cyelic estragen & progesterone (pregnancy is impossible) > Dysgenstic ovariese.g. Tuer syndrome ~ Complaint: primary amenorthea, no secondary sexual characters + Diagnosis ™ Phenotype: characteristic features = Karyotype: 45x0 oF mosaic (ASxo146x« OR 45x0/46xy) * Ovaries: streak (ibrous) gonads = Treatment: HRT (pregnancy is impossible except if mosaic) > Accessory (supernumerary) ovary: no complaint (usually found in the broad ligament) > Abnormal descent: vary rare (the ovary found in high position) © Fallopian tubes > Aplasia:infotity (aplasia of uterus) > Hypoplasia: short, totuous, narrow: leads to inferity or ectopic pregnancy > Accessory ostia diverticulum: may lead to infertity or ectopic pregnancy © Convix > Corvical atresia = Complaint: ceyptomenorrhea & cyclic lower abdominal pain = Diagnosis: inabilly to inlroduce uterine sound through the cervix = Treatment: dilatation and surgical correction (dificult) > Patulous intemal os <> repeated pregnancy loss > Congenital elongation of the portiovaginalis = Complaint: nothing (dysparuenia after marriage) Must be diferentiated from supra-vaginal elongation in prolapse Treatment: surgical amputation if symptomatic SS> Aplasia: (Mlullerian agenesis): primary amenorthea, infrt > Hypoplasia * Types: + Rudimentary (very small slid organ) * Infante (‘ati of body : cervix = 1:2) * Pubescent (rai of body : oerv * Complaint "Amenorthea or hypomenorthea = Intetity or recurrent pregnancy loss * Diagnosis “Uterine sound Uterine index = Corporal length / (Cervical length x2) serine hypoplasia Is ciagnased i= 0.75, 2, Utrasound (or 3D is beter) 5. SG (Hysterosalpingography): a small cavity 2. Hysteroscopy Treatment ~ Cyclic estrogen and progesterone to increase uterine size (ficult) = Ceretage is done during pregnancy ” » Fusion defects 1- Uierus didelphys: 2 bodies, 2 cervices, 2 vagina (vaginal septum) 2. Uterus bicomis bicollls: 2 bodies, 2 cervices 3 Uterine bicomis unicolls: 2 bodies, 1 cervix 4: Seplate & subseptale '5- Arcuale (uterus cordiformis) @ depression at the fundus {6 Unicornvate (complete arrest of development of one Mullerian duct) 7- Rudimentary horn (under-development of one Mullerian duct) Itmay be communicating or non-communicating (blind hom) * CIP Usually asymptomatic (discovered during search for pregnancy failure) = Spasmodic dysmenorthea may be more comenon = Slight increase in menstrual flow (menorrhagia) in double uterus * Complications + Eatly pregnancy © Vagina > Vaginal aplasia * May be present alone OR ‘More commonly with absent uterus: Mullerian agenesis (Mayer-Rokitansky-Kustor-Hauser syndrome) ‘* Commonly associated with Renal (30% ) & Skeletal (15%) anomalies Features = Karyotype: normal 46% = Phenotype: normaly lookin female = Gonad: ovary = Hormones produced: estrogen Internal genitalia: nothing present = Extemal genitalia: a vaginal pouch + Should be differentiated from Testicular feminization syndrome = Treatment 1. Frank method: progressive dllators are used by the patient 2. Vaginoplasty: ~ Melndoe's operation: dissection between bladder & rectum ‘Amouldis then inserted in the vagina to avoid adhesions ‘An amnion graft may be used also =. Wiliams operation: surgical creation of a labial pouch 3. Colon Vaginoplasty (abdominally) + skin graft or amnion graft 4, Laparoscopic Vache! operation (gradual traction ofa ball vaginally via laparoscopic inserted threads) > Longitudinal vaginal septum * Duplication of ulerus may be present = Asymptomatic condition or may lead to dyspareunia or obstructed labor if breech overrides septum during breech delivery | > Transverse vaginal septum ‘= Upper: between the upper & middle % of the vagina + Lower: site of fusion between Mullerian ducts & urogenital sinus upper 3/4 & lower 1/4 ~ > imperforate Hymen * Due to failure of complete canalization of the vaginal plate * Leads to cryptomenorrhea (false amenorrhea) '* Imperforate hymen is bluish & bulging but transverse vaginal septum is thicker > Congenital Vesicovaginal or Rectovaginal Fistula —- KDI um|- Genital ge: (1) Infundbulo- eM Higament. (2) Ovary (3) (Ovarian game. (4) Reund oament -Wolien Duct Sytem: (a) Pronepivic tubules. (2) Gontal tubules. (c) Mesonephros. -Malleian Duds: () Fmbriae (i Fallopian tubes.) Uterus. (vagina = UGS: Uogental sinus ‘of gubernaculum inthe female Gubernaculum testis Gubernaculum in the femaleDevelopment of the extemal genitalia in both males and femalesrate hymen Hematocolpos / Hematometra Longitudinal vaginal septum Bicomuate uterus |___Unicomuate uterus (SG: Uterine septum (HSG: a ,Physiolegy of Menstrual Cycle # © Follicular phase: (days 1-13) tis the phase of maturation of ovarian follicle. Over 400 primitive oocytes ‘enter the growth phase each cycle and migrate towards the surface of the | ovaries. Only 4-5 folicies continue to mature, the remaining follies become atrelic. Ideally one-two ova reaches maturity each cycle. > Primordial follicle (50,1) ~ Primary oocytes surrounded by single layer of pre-granulosa cells + And are arrested in prophase of first meiotic division > Proantral follicle (2001) ~ FSH stimulates follicular growth -> Pre-granulosa cells become cuboidal and proliferate to form several layers of granulose cells (membrane sgranulose). = These cells wil increase E2 production that stimulates formation of more FSH receptors -» more follicular growth (vicious cycle) ~ Zone pellucida Is a hyaline membrane formed now around the ovum, and limit, further increase in size. Fluid spaces (liquor folicul) start to appear between the granulose cells Theca interna develop by the surrounding parenchymal ces. ~ Granulosa cells can't produce estrogen alone. The Two coll theory involves Integration of both granulosa & theca cells to produce E2: 1. LH stimulates ‘androgen’ in theca cells 2. FSH ->» stimulates ‘estrogen’ synthesis in granulosa cells (by ‘aromatization of androgen produced from theca cells) > Antral follicle ~ The fluid spaces between granulosa cells join together to form a large antrum {ull of estrogen. This high E2 (+ inhibin) -> inhibit FSH thus decreasing ‘aromatization & increasing local androgen -» atresia of most follicles ~ The antral follicle (the dominant folicie) is immune against this atresia as it has the largest number of FSH receptors inhibin: A peptide produced by granulosa cells that attenuates FSH production and enhances LH-induced androgen synthesis, thus | the dominant follicle can continue development and other follicles | i undergo atresia. Aciivin: A peptide produced by granulosa cells and the pituitary gland that augments FSH production, an action almost directly 10 that of inhibin. > Preovulatory follicle (18-24mm) Here, the oocyte resumes the prophase of meiosis | -> haploid (14) no of chromosomes + frst polar body ~ Meiosis I (mitotic ike) occurs upon fertilization -> mature oocyte & 2nd polar bot - <2© Ovulation: 13-15 “the tertile phas > The mature Graatfian follicle (the dominant folcte) one or more, will open and release the oocyte and the folicular fuid into the peritoneal cavity {ayers of mature Graafianfolicle = Ovum Perivitelline space. Zona pellucida + Corona radiata... Cumulus Oophorus....Antrum follcul © Membrana granulosa....Theca intern......Theca externa >» Porsistent elevated estradiol more than 200 pg/ml for more than 50 consecutive hours will simulate @ positive feedback on LH with a resultant LH surge = ovulation within 36 hours. = There is also a smaller FSH surge (2nd surge) to increase LH receptors >» LH stimulates androgen production theca cells to: ~ Ensure complete atresia of the non-dominant flicles = Increase libido at mideycle “+ The mid-cyelic surge in LH is short-lived due to "Exhaustion of the LH storage inthe pituitary = Loss ofthe +e feedback stimulus of £2 > Mochanism of extrusion of the ovum Is unknown. Theories include:- Proteolytic enzymes (collagenase, hyaluronidase) = Contraction of ovarian smooth muscle (by prostaglandin) © Pressure effect of the antrum folicul Luteal phase: 14 days ‘+ Corpus Lutoum (CL) formation 1] Proliferative stage <> Granulosa & theca cells multiply rapidly 2] Luteintzation stage < deposition of cholesterol -> yolow vacuolated ‘calls very actively involved in steroidogenesis of both ‘estrogen & progesterone (peaks within a week i.e. day 21) Granulosa calls ~ lutein cells + Theca cells -» paralulein cel 3] Vascularization (mature CL) + Fate of corpus luteum (CL) 4] no pregnancy <> Retrogression: Estrogen & progesterone from CL.» ~ve feedback on LH FSH; thus CL starts degeneration at the 22nd day with formation of corpus albicans then corpus fibrosum, ss Drop of both steroids will induce menses together with release ofthe -ve inhibition on LH & FSH —> 7 LH & FSH. thal stimulates the commence of a new cycle 5] lf pregnancy occurs «2 CL of pregnancy: Fetal trophoblast wil produce HCG -> stimulation of more ‘growth of CL (hypertrophic, larger, cystic) with maintaining of high E2 & progesterone till 12 weeks (tll placenta forms) ep© The proliferative phase ~ This phase coincides with the follicular phase of the ovarian cycle (due to the effect of estrogen produced by the growing follicles) = It starts with shedding of the endometrium at _menstruation; and is ‘characterized by both glandular epithelial and stromal growth 4. The epithelium changes from a single layer of low columnar cells to ppseudo-stratified epithelium with frequent mitoses 2. The stromal component ofthe endometrium also expands rapidly 3. Endometrial thickness grows from 0.5 mm at the end of menstruation ‘to about 5-8 mm atthe end ofthis phase © The secretory phase The secretory phase of the endomelrium colncidos with the luteal phage of ovarian cycle (due tothe effect of P and E2 produced by the Cl. - It starts shortly ater ovulation till menstruation starts; and is characterized by endometrial glandular secretory activity 1. Progesterone inhibits estrogen induced cellular proliferation restricting the depth of endometrial thickness; while endometrial glands continue to grow leading to increased tortuosity of both 3nds and spiral arteries in order to fit in the endometrial layer. 2. In the early secretory phase; shortly after ovulation, vacuoles containing subnuciear intracytoplasmic granules appear in Glandular cells, These vacuoles progress. to the apex of the landular cells and thelr contents are released into the endometrial cavity 3. In the mid-secretory phase; peak secretory activity occurs at the time of implantation, seven days afer the LH surge (mid luteal phase), with associated stromal edema, Within the endometrium large granulated lymphocytes predominate which may play a role in regulating trophoblastic invasion during implantation if [pregnancy occurs (through natural kiler -NK~ cals) 4. In the lato secretory phase; three distinct zones of the endometrium ‘can be seen Z “yathiaoss | | Stratum spongiosum. (around gland bodies). thickness | cum. (around gland necks). Y4thekness © Menstruation ~ Degeneration of CL 1. Premenstrual sharp and rapid dectine of progesterone will result in ‘shrinkage of endometrium & decreased edema -» colling of spiral arteries (up to 8 loops) 2, Breakdown of endometrial lysosomes will reloase prostaglandins (esp 2a) resulting in further vasospasm & myometrial contraction 3, This leads to severe ischemia of spiral vessels for 4-24 hrs and necrosis of superficial and intermediate layers only -» shedding of tendometrium & opening of vessels follows -> massive blood loss. eSes = Menstrual blood -» stops due to: 4. Vasoconstriction (mainly) & haemostatic plug formation 2. Regeneration from zona basalis (protected from the monthly shedding ‘as itis supplied by the basal arterioles ~hormone insensiive-) Normal menstruation “Rhythm [regular every 21-36 days | <21 =polymenorthea |> 38 = oligomenorrhea Duration | average 3-5 days - <2 = hypomenorthea ‘amount | 60-80 ec (2 napkine May) | = Composition ‘Mainly blood, endomotrial shreds, FOPS, leukocyte mucous, desquamated vaginal epithelium, bacteria, + Normally 75% arterial blood & 25% venous blood + Normally menstrual shedding forms clots inside the uterine cavity but due to the fibrinolytic activity it pass outside as fuidy blood Follicular phase (EZ effec) | __ Lulteal phase (P effec maximum at ovulation ime _|_maximum 1 week ater ovation eanty viscid (dry) =e (no-arborization) (non-stretchable) viscid, hick ed | Decreased + Forming test: Mieroscopie examination of a drop of cervical mucus left to dry for 10 ‘minutes on a glass slide in the folicular phase wil reveal an arborizing palm leaf patter; (due to its high NaCl and KCI content: E2 effet). In the luteal phase the arborizing pattern is lost giving a -ve test. + Spinbarkoit test is positve when the cervical mucus can be drawn between two ‘slides into threads stretching up to 10 cm due to high mucus content in response to high estrogen levels Studied by vaginal smear (exfoliative cytology) from posterior fomix~ Comification Index denotes the hormonal state. Maturation index calculates the ratio of basel, intermediate, o superticial cells on vaginal cytology Follicular phase (€2) Luteal phase (Progestoron + Superficial cels (polygonal) ~Intermedite cells (naviutar) + Acidopilic (esinophic) cytoplasm deus (sal, dark) Few lymphocytes “Basophilic cytoplasm Clear (vesicular nucie ‘Many lymphocytes Maturation index 0-70> Types + Estradiol (£2) -» most potent, most important + Estrone (Et) > less potent, estrogen of menopause * Estiol (E3) > least active, produced in large amounts in pregnancy > Source ‘© Glands <> ovary (ollcles & CL), placenta, suprarenal cortex + Peripheral conversion <2 of androgens (30% of E2) > Metabolism: 99% bound (SHBG)... metabolized in liver * Metabolic + Protein -> anabolic with nitrogen retention * Lipid — protective effect against IMD (7 HDL + 4 LDL) = CHO —+some antl.insulin action * Coagulation +t thrombosis (* cloting factors + | fibrinolysis) * Bone <= stimulates osteoblastic activity -> growth spurt then closure of ‘the epiphysis. Butt sill protects against osteoporos * Endocrinal system * Pituitary gland: -ve feedback on FSH, +ve on LH -> ovulation * Breasts: Stimulates duct system mainly + 7 vascularity +7 fat In pregnancy > 1 prolactin release but blocks its action * Increases all binding globulins (SHBG, TBG, CBG) 2: Local -qenital effect * Vulva & vagina => crease vascularity, size & deposition of fat * More deposition of glycogen: Doderrein's bacilli forms lactic acid * Corvix <2 secretion becomes fuidy, alkaline -> +ve Spinnbarkeit & Fem * Uterus 62 proliferation & hyperplasia + increased vascularity * Tube 6? Increased vascularity, hypertrophy of muscles + * peristalsis Contraception = e.g. in contracoptve pills Inferlty = to improve pattem of cervical mucous (if using clomiphene citrate) Infections =» to improve healing (postmenopausal vulvovaginitis trophic ulcer, vulval dystrophy) Some menstrual disturbances ~» DUB, dysmenorthea Menopause =» ERT (Estrogen Replacement Therapy) usually with progesterone — <> we veal> Types + Natural progesterone....micronized + Synthetic... liferent generations (look COC) > Source <= Ovary (mainly rom CL), placenta, suprarenal glands > Metabolism <> bound to SHBG... metabolized in lver(pregnandiol) > Actions. A Extra-genital effect ‘Thermogenic (incteased BET) * Stimulates doop respiration (esp in pregnancy) * Relaxes smooth muscles (e.g. GIT & ureter) ® Salt & water retention * Breast -> stimulates alveolar system development in breast * pituitary -> -ve feedback on FSH & LH (inhibition of ovulation) 2+ Genital effect * Vagina <2 Reduce thickness of epithelium (thus reducing acilty) Reduce maturation (inceased intermediate calls) cervix <> less secrotions: vised & cellular with -ve Spinnbarkeit & Fern test * Uterus -Endometrium -> . Change proliferative to secretory “In pregnancy: decidua formation Prolonged use leads to atrophy -Myometrium —> hypertrophy & decreased tone & motility * Tubes + decreased motlity > Uses 1 + Threatened abortion * Corpus luteum insufficiency * Recurrent pregnancy loss + Surgery during pregnancy 2 Gynecology Endometviosis = Endomatial hyperplasia = Endometial earcinoma 3% ttstwogenin = HRT, some amenorrhea cases = DUB (dysfunctional ut. Bloeding) = PMT (Premanstrual tension) = COG (Contraceptive pills) Bg> Metabolism > Action > Uses (not preferred due to its anidrogenic side effects); but may be used in ‘Anatomy of the pituitary gland = Bound (99%) to SHBG & albumin = Only 1% i free *= Testosterone will attach fo its receptors in the hair folicle; then by the action ‘of Su-reductase it will be changed locally to the more potent DHT (cinydro-testosterone) + Normally the level Is t00 low to cause any effect * However its essential for axillary & pubic h female libido *= But it may increase (e.g. PCO & androgen producing tumors) leading to: ~ Anovulation & inferlity + Hirsutism + Defeminiztion followed by viiization production and the normal * Vuival dystrophies (atrophic types) * Some sexual disorders (with decreases libido) “Lies inthe sella turcica + Covered by diaphragma sellae which is pierced by the pituitary stalk (carries vessels & nerves from hypothalamus to pitultry) ‘Lies behind the optic chiasma On each side there isthe cavernous sinus ‘* Below ilies the sphenoid bone Parts of the pituitary gland [Anterior Tobe (adeno-hypophysis) [Post lobe (neuro-hypophysl Origin | Rathke’s pouch (upper part of pharynx) | Down growth from diencephalon Controt Portal circulation Nerve fibers [Egy Porte ctreuiation - - Hormone | Acidophil | Basophil_[Chromophobe| Oxytocin & ADH Produced) —crsath | FSH *LH + Reserve celle, Forme in hypothalamus Tomene| TSH. | Moyrotease, | £28 song _ amore) TSH, -Mayrelease | Store & released rom pita> Source = FSH, LH are secreted by the anterior pituitary (basophils) + HCG is secreted by trophoblast (also produces some FSH & LH) * They pass to blood free (unbound) as they are released in litle amounts > Chemistry They are all glycopeptides having similar a-chains, different p-chains + Soin cases of assay of HOG we do f-subunit assay > Actions. Stimulates development of follicles Increases FSH & LH receptors Stimulates steroidogenesis in granulosa colls FFSH surge Is important to stimulate formation of LH receptors Control is by negative feedback by estrogen and progesterone (Qhrough inhibin) ~LH = LH surge causes ovulation = Stimulates steroidogenesis by theca cells ~ Responsible for luteinization of theca & granulosa cells HCG = Similar to LH = Maintains corpus luteum in pregnancy til placental ‘steroidogenesis is suficiont (al 12 wk). Important for proper spermatogenesis in male fetus > Uses © FSH & LH induction of ovulation in: 41. Hypothalamic failure, ptultary failure, clomiphene induction failure 2, Unexplained infetity 3, Assisted reproductive techniques (ART) 4. ‘Male infertilty HCG = 41. Ovulation (LH like activity) given as 5.000 ~ 10,000 IU / IM 2. Corpus luteum insufficiency 3. Some cases of threatened abortion (instead of progesterone) a 4ea i| [ Gonadotrophin Releasing Hormone Gu) | > Function "GnRH (previously LHRH) is a decapeptide wiich stimulates "synthesis & storage of Gn (reserve poo!) “induce immediate release of gonadotropins (releasable poo!) © GARI is released in pulsatile fashion (every 60-90 minutes) > Controt ‘© Negative feedback loops + Long feedback loop by ovarian steroids Shart feedback loop by Gonadotophins 1 Ultrashort feedback loop: GnRH inhibit its own release © Neurotransmitter control on the Hypothalamus + Noradrenaline: increase GnRH pulsatility 1 Dopamine, serotonin, prendorphins reduce GnRH pulsatilty > Uses of GnRH analogues Gavi asal spray 22 Nafarelin (synarel)... Buseretin (supertact) SC injection <2 Goserelin (zoladex) © Iivinjection <2 Triptorelin (decapepty)...Leuprotide (lupron) 1) used in pulsatile manner = induction of ovulation (with no risk of OHSS) 2) Mused in continuous manner w ‘Bown regulation of pituitary receptors: inhibition of FSH & LH —» ‘reducing estrogen. therefore used for ~ jnhbition of premature ovulation in ART {Some estrogen dependant tumors: fibroids, endometrial hyperplasia, endometriosis and adenomyosis = Dysfunctional uterine bleeding 1 Idiopathic precocious puberty = May be in idiopathic hirsutism ‘= Thus its main side effect is production of a pseudo-menopausal ‘Sate especially osteoporosis. Add Back therapy of low dose ‘estrogen and progesterone may be given to avoid this. Follicular phase| uteal phase | [30-75 pgimi 200-300 palm Harmon om 02-0.8ngid z levels Gonadotropin | FSH— 5:30 miUil 1 LH 5-20 mim 2-20 ngimi JHormonal cyclic changes. Maturation of the L ‘The ovarian cycle >|Puberty‘Age of transition from childhood to adulthood physically ending in full sexual & Teproductive development. The mean age of onset of puberty Is about 10.5 years of ‘age in gifs and 11.3 Years in boys. The normal range for pubertal onset is between Band 12 years in gifs, and 9 to 14 years in boys. # Before puberty > There Is no/very little estrogen secreted due to: ~ GnRH suppression (unknown, mostly controlled by a gene in GnRH nucleus) ~ Very sensitive HPO axis to ve feedback of steroids > Determinants of pubertal timing: = Genetics accounts for the majority of the variability in the timing of pubertal ‘onset. The ming of puberly and menarche in a girl is best predicted by the timing of menarche in her mother. = Constitutional factors ~ Paychological factors ~ Body fat and leptin, activity (athletes have later puberty) ~ Melatonin release from pineal glands > Somatic changes = Growth spurt [peaks at 11 yr followed by ‘closure of epiphysis ~ Deposition of fat leading to feminine round ‘contour ~ Persistence of high pitched voice > Secondary sexual characters ~ Adconarche is the activation of the adrenal cortex for the production of ‘renal androgens, and typically occurs before the onset of puberty = Gonadarche isthe activation ofthe gonads by the pituitary hormones folide: ‘stimulating hormone (FSH) and luteinizing hormone (LH) ~ Pubaicheis the appearance of pubic hair * ‘Thelarche is the appearance of breast buds. In most gis, the earies! ‘secondary sexual characteristic Is breastlareolar development, alhou 2 substantial minority have pubic har as the inal manifestation = Menarehe occurs 2.6 years after onset of breast and 0.5 years after ped height velocity. Ik is the last event (usually the intial cycles ‘anovulatory) > Genital changes due to inereased estrogens with development ofthe reproduc ‘organs —— co,stages) for pubic hai, breast, and genitalia development ‘Stage 1; Prepubertal Stage 2: Breast bud stage with elevation of breast and papilla; enlargement of areola Stage 4: Areola and papila form a secondary mound above level of breast Stage 5; Mature stage: projection of papilla only, related to recession of areola 2; Further enlargement of breast and areola: no separation oftheir contour > Pubic hair Stage 1: Prepubertal (the pubic area may have vellus har, similar to that of forearms) Stage 2: Sparse growth of long, sight pigmanted hair, straight or curled, along labia Stage 3: Darker, coarser, more curled hair, spreading sparsely over junction of pubes Stage 4: Hair aduttin type, but covering smaller area than in adull; no Stage 5: Adult type, with horizontal upper border & spread to medial surface of thighs f Abn EM ‘© Congenital <> ambiguous genitalia (intersex) esp congenital adrenal hyperplasia © Traumatic <> circumcision, sexual abuse, accidental trauma, foreign body © Inflammatory <> prepubertal vulvovaginitis © Neoplastic = ovary (germ call tumor), vagina (sarcoma botyoids) © Vaginal bleeding “Slight bleeding may occur in the 1st week (neonatal / birth crisis) “Traumatic -» foreign body = Inflammatory — Pre-pubertal vulvovaginitis (the commonest cause) Neoplastic > the most serious cause “Before puberty -» Precocious puberty AL puberty -> dysfunctional uterine bleeding(0 Delayed puberty] The absence or incomplete development of secondary sexual characteristics © Bounded by an age at which 95 percent of children of that sex and culture have initiated sexual maturation » Nomenarche by 16 > No secondary sexual characters by 14 » No menarche for 5 years after completed thelarche 8 Etiok > Primary hypogonadism - High FSH / LH 41. Gonadal dysgenesis (Turner syndrome — 45x0) 2, Ovarian failure (autoimmune or post-infection’ trauma! surgery) > Secondary hypogonadism - Low FSH J LH 4. Disoases of the hypothalamic-ptuitary axis (as in amenorthea) 2. Hormone deficiencies: hypothyroidism, hyperprolactinemia, DM, Cushing 3. Neoplasms: e.g. pituitary adenomas 4, Severe malnutiton (starvation / anorexia nervosa) 5. Extensive training as athletes / acute ilness, severe stress > Constitutional delay in GnRH pulse gnerator (50% of causes) # Evaluation > History: patient grown pattem, nutritional habits, associated congenital anomalies, presence of family history > Examination: standing height & arm span, secondary sexual characters (Tanner) > Investigation: ~ LHL ESH measured at any ime = Hyper-gonadotrophic (FSH > 30 mlU! mL: karyotyoing Hypo-gonadotrophic (FSH < 10 miU mL): CT skull ~ Normo-gonadotrophic:ullrasound pelvis ~ Additional: thyroid funetion tests, serum prolactin > If cause is found... thyroid hormone replacement or dopamine agonist for lactoroph ‘adenoma or excision of craniopharyngioma > For constitutional cases: watchful expectancy for spontaneous resolution...or: ~ Estrogen for 2 years followed by cycic estrogen and progesterone = Role of gromth hormone therapy is controversial Main Pathological causes of Short Stature 41. Hypothyroidism 2, Cushing's syndrome 3. Adrenal hyperplasia 4. Turner's syndrome,[@ Precocious puberty (PP)] Definitio ~ Appearance of any pubertal changes eatir than its mean by 2.5 SO ‘Approximately:-< 8 years for thelarche & < 10 years for menarche Etlolosty Isolated (Incomplete) = premature thelarche (unilateral or bilateral) with/without other secondary sexual characters (premature Adrenarche) Reassure the patient (ther is no tin E2). tis just local tissue sensitviy; and other pubertal changes usually occur normally > Complete Isosexual (ME2) qe Gonadotrophin dependent | Gonadotrophin independent | (excess androgen) True (central) PP- False (peripheral) PP- very rare] {Ueiopathic! constitutional 1-E2 secreting ovarian tumors | 1- Androgen secreting the commonest cause (80%) 2 Iatrogenic (exogenous drugs) | ‘mors whether: | due to 3-Primary hypothyroidism ~ Ovarian | ary maturation ofHPO ax 4 ume Aight a Wad of-| HE | 2-Organie brain lesion ~ Precocious Puberty pean | ‘vauima I tumors |meningitis | ~ Polvostotic fibrous dysplasia | Cushing syndrome | that stimulation of HPO axis |__~ Caf6-au lit patches 4-adreno-genital $ | al ovulation occurs |. No stimulation of HPO axis | (Congenital adrenal + Normal ovulatio No stimulation of HPO pros one {Pregnancy can occur. No ovulation (only feminization) | _ "P&P | Assessment ® History Growth paltem & development since birth / behavioral changes at time of puberty | presence of headache or abdominal pain / usage of drugs / family history of early maturation / past history of surgical operation > Examination ‘Stature / weight / body contour, hirsutism / acno; breasts / extemal gonial neurologic / endocrine (optic fundus, visual field, Sense of smell, thyroid). > Investigation 1) Bone age 2) Hormonal assay 3) FSH&LH “olarded > hypothyroidism ~ High androgens heterosexual High True -» CT brain ‘Normal age -> isolated PP * CT abdomen: adrenal tumor —Low- False: Advanced + homonal | Pelvic US: ovarian tumor * Pelvic UIS. | effect (Isosexual or *47-OH progesterone: CAH * TSH, tree T3,T4 heterosexual PP - High estrogens isosexual * Bone scan (McCune | therefore measure FSH & LH Albright $) Ireatmes “The primary goal of therapy is allow a child to grow to @ normal adult height" 1. ta cause is found e.g. surgery for ovarian tumor, thyroxin for hypothyroidism 2. idiopathic =» GnRH analogues continuously til age of 12 (to suppress HPO axis) .#2 Definition It is the permanent cessation of menstrual periods, determined relrospectively ‘after a woman has experienced 12 months of amenorrhea without any other ‘bvious pathological or physiological cause. ILoccurs at a median age of 61.4 years in normal women, and is a reflection of complete, or near complete, ovarian follicular depletion, with resulting hypoestrogenemia and high FSH concentraions F Gnaaarc © We varatonal peiod dure which the Tenaie pases Wom We reproduetvetopstimenopa vel stage 45-52] ‘Sr bermangaguse period of Me erund menopause (before 1 yea after) ‘3 Postmenopause <> perod of fe after 1 year from FMP (final menstrual period) ‘2 prematuremenennsa = primary ovarian insficency before 4 years he Antificial pause 2 induced surgically / medically / or by irradiation + Hormonal changes Reduction in £2, inhibin B. AMH, antral olcle count (AFG) du to exhausted ovarian follcies however E1 (the main postmenopausal estrogen) is produced by Peripheral conversion from androstenedione in fa, liver and skeletal muscles > Rise in FSH and LH due to the loss of -ve feedback of sex steroids Testosterone continues to be secreted (adrenal -75%- & ovary -25%) by the same Tevels 28 before menopause therefore there Is a relative increase of testosterone ‘over estrogen as compared with the premenopausal Ife + Menstrual changes Women typically first notice a lengthening in the intermenstrual interval (in contrast to the ‘shortening that occurs in the late reproductive years), Then more dramatic menstrual cycle changes with skipped cycles, episodes of amenorrhea, and an increasing frequency of anovulatory cycies. This lasts for 1 to 3 years before the final ‘menstrual period (FMP) # Menopausal symptoms 11 Vasomotorinstablliy <> hot flashes flushes) 60-85% ~ Sudden sense of heat & flushing in face, neck and chest due to attacks of ‘vasodllatation (palpitation & sweating} folowed by cold shivers = Each attack last for few seconds up to few minutes. it may be repeated from ‘wice /day up to ane thowr. = ‘They occur more frequently at night (night sweats). Mostly they are due t hypothalamic instablity associated with FSH fluctuations, 2) Genitourinary < due to loss of estrogen integity to the genitourinary system = Discharge (senile endometrits & vaginitis), pruritus = Byspareunia (dryness of vagina) = Dysuria, Frequency, urgency, SUI, recurrent cysts 3] Gi symotoms => dyspepsia, flatulence, change in appetite > 4[ees 4 Skia <2 mild hirsutism (upper lip & chin) 5] Paychological <> depression, iritablliy, anxiety, Insomnia, decreased libido 61 Lona term consequences * Cardiovascular «= coronary hear disease, hypertension ~ Loss of estrogen leads to Increased LDL (dangerous) & reduced HDI. (protective) Atheroscierosis (deposition of cholestercl) > hypertension - Predisposing factors: positive family history, diabetes, obesity * Osteoporosis <2 rheumatic joint pains, backache, dowager hurnp - Definition Its the progressive systemic bone resorption leading to lass ofthe bone mineral density (BMD), Subsequent, there Is susceptibility to fractures spin cancellous bones (Lumbar vertebra, femur neck, distal radius) (O:teomalacia = softening of bones due to defective mineralaation Ca" &P] Dsteoporosis ® retuction of BMD {matrix & minerals <-2.5 SD) Leading to: micro-archivectural deterioration [Osteopenia = reduction of BMO with score between -1 and-2.5 5D - Physiology Peak bone mass is acquired at 25-30 years, ator that rate of bone loss rises from 0.5% iyear up to 2-3 % In the post-menopausal Iie. Estrogen deprivation leads to osteoclastic activity exceeding osteoblastic one. ~ Risk factors Positive family history, cigarette, alcohol, sedentary life, stim, white races Chronic tver or renal, drugs e.g. (steroids, heparin, thyroxin) # Diagnosis of menopause > To Confirm 1. FSH > 25-40 miUimL (but not recommended to be routinely assessed jpresence of menstrual regularities & hot flashes is more important) 2. Historically = E2<20 pgil.....not necessary - Vaginal cytology...decreased superficial mature calls less than 5% > For osteoporosis 1. DEXA (Dual Energy X-ray photon Absorptiometry): Osteoporosis is diagnosed ‘when BMD is < 2.5 standard deviation (SD) as compared to young adults (T-scoréfIts the gold standard in diagnosing osteoporosis 2. Ultrasound: done on calcaneous, head of humerus (DEXA is better) 3. Historically - Plain X-ray (needs loss more than 40% of BMD to diagnose osteoporosis) - Biochemical markers in urine (as some urinary collagens) > For coranry artery disease: total cholesterol, HDL, LDL, triglycerides a 74 Indications 1. Sympioms of estrogen deficiency (menopausal syndrome) 2. Asymptomatic women with high risk for osteoporosis / coronary heart disease 3. Premature ovarian insufficiency ‘# Contraindications Recent myocardial infarction Recent / active vascular disease “poorly controled OM ‘Thrombophiebits, ‘# Mechanism of action > Protection from osteoporosis by ~ Reducing action of osteociasts (through inhibiting effect of parathormone) = Inereasing calcium through (Increasing GIT absorption, reducing renal loss ‘stimulation of caletonin, activation of vitamin D) > Protection from CVD by ~ Increasing HDL, reducing LDL & cholesterol = Reducing cholesterol deposition in vessels + vasodilatation = However; these actions are recently masked by the rise in cardio-vascul ‘accidents for HRT users +# Consultation needed before HRT History taking <> to exclude contraindications Physical examination => Blood pressure, weight, breast / pelvic examination) Investigations: = General <> blood sugar, ipid profile (+ liver function tests) = Local = mammogram, Pipelle & Pap smoar (if genital bleeding) 4 Administration > Estrogens Only (ERT) only given Ifthe uterus is removed © Ona. ruerary = Conjugated equine estrogen (CEE - Premarin): 0.625-1.25 mg fd + Esttiol (Ovestin) 1 mg /day Nowonat 41Skin patch (estraderm) > applied twice weokiy (0.05 mg) ; 2] Skin gel (estrage!) applied twice daily to arms or legs 3] Vaginal Cream (premarin) > for atrophic vaginlis & dyspareunia 4] Subcutaneous Implant mg -> inserted in abdominal wall / 6 m 4> Combined E & P therapy (HRT) ~ A progestogen must be added ifthe uterus Is present to prevent harmful ‘endometrial effects (hyperplasia J carcinoma) Itmay be given alone to relieve hot flushes # Reaimens 1. Cycle (sequential) CEE 0.625 mg/day + MPA 10 mg fd for 10-14 days, = But leads to cyclic withdrawal bleeding 2. Confiavous = CEE 0,625 mg + MPA 2.6 mg daily = Itavoids withdrawal bleeding RECENT VIEW IN Benefits / Risks of HRT WomenHealthinitiative: WHI seudy-) Effect Definite 4.75% in symptoms. However, ty to use HRT benefit for tushes for minimal time as possible 5% in Bono density, 130% in fractures. However, ty {0 use other allerative. non hormenal drugs for osteoporosis Signcantt 2-40) Detnte |-Encometriat cancer _| Deereased by adding ‘progesterone ‘tsk |-Venous thromboembolism) Significant 24x). Decreased by screening fot hereditary defeieney of eoting factors ~ Cardiovasc disoase | Signifeant?. Therefore no HRT should be ‘sed for primary prevention of CHO Breast cancer Slight statstca increase Probable| Related to length of use (esp if > than 5 year) racist? | Estrogen protec the normal breast cells trom malignant change butt may 2 enhance the growth of some types of already existent malignant cells. ‘The other problem Is thatthe highest incidence of breast cancer occurs in old ages (le inthe age group who wil receive HRT: some sort of bias) Wo proven | Quality oe, dementia, cognitive function, sleep, depression, sexually effect 7 * Starting rom recommending HRT at any age after menopause (never too lal!) * Reaching the recommendation never to use them more than 2 years. + Till the recent concept that non-hormonal drugs are better used a Eee ,Nonhormonal therapy > SERM = Selective Estrogen Receptor Modulators (agonist antagonist) are drugs \which stimulate diferent estrogen recoptors(a,). Therefore:- - Exert estrogenic effects on desired tissues (CVS & bones) + Avoids estrogen stimulation on others (uterus, breast) ~ Commonest drugs are Tamoxifen & Raloxifen » Tibolone (Livial) + Synthetic steroid with weak estrogenic, proaestogenic, androgenic effect Good relieve of menopausal symptoms (hot flushes & osteoporosis) Advantages: ‘Weak estrogen doesn't stimulate uterus or breasts Progesterone is already present (no need to be added) ‘Androgen also improves liido = Dose -» 2.5 mg tablet day » Eorhot fushes = Agreal, bromocriptine (dopamine agonists) + Clonidine patch (twice weekly), « methyldopa Phyto-estrogens (isa natural 'E2' found in soya boans) » For osteoporosis > Prophylaxis «Cessation of smoking & alcohol + Reguiar weight bearing exercises + Adequate intake of Ca & vt D form adulthood. Calcium -» 1000 mg dally Vitamin D> 800 IU dally > Non-hormonal therapy 1. Bisphosphonates (inhibit osteoclasts <> decrease bone resorption) They are the most potent + increase BMD by 10% after 1 year Alendronate (Fosamax) -» 10 mg /day of 70 mg once weekly 2. Clacitonin (trom salmon) = intranasal spray 200 IU (miacalcic) 3. Fluoride <> the only known osteoblastic crug -historieal importance 4, Teriparatide LM. for2 yrs <2 anabolic bone effect ~recent~ > Estrogen + Conjugated equine estrogen (CEE} 0.625 mg daily or SC E2 implants (1g) * Given mainly for the frst 10 yrs (max rate of bone loss). But if HRT is stopped -» rebound bone loss - Moreover; due to the many other health hazards of HRT; itis ne tanger recommended as a primary line of therapy for osteoporosis > Forthose at isk of coronary heart disease <> Statins / Juspirin 81 mg daily > For vaginal atrophy < lubricants / vaginal Premarin cream (CEE) SF1G horty & menopause eS Loss of labial and vulvar fullness Postmenopausal non- year oldfemale hormonal thera, Normal looking cervix | Post-menopausal cervix (multiparous) {atrophic Deterioration of vertebral support , Osteoporosis Osteoporosis (ullra-structure)#8 Definiti Amenorrhea is the absence of spontaneous menstruation ‘ Hypomenorttiea is scanty menstruation: either decrease in amount (less than 30 rior duration (ess than 2 days) 4 Oligomenorthea is infrequent menstruation (length of the cycle more than 35 days) | Both hypo‘oligo may be constitutional or endocrine in origin. Should be | Investigated & treated samo as in amenorthes: but prognosis is better '¢ Physiological - Before puberty: as gonadotrophin secretion not ye established - After menopause: due to exhaustion of ovarian follicles ~ During pregnancy: contiauous placental steroid production = During lactation: as prolactin inhibits GnRH, inhibite affect of gonadotrophins on ovary and inhibits ovarian steroidogenesis ¢ Pathological....primary or secondary Definition absence of menses in a patient who has never menstruated before, either at: 14 years with absence of secondary sexual characters, ‘orat 16 years if secondary sexual characters are present = Imperforate hymen (the commonest cause) = Transverse vaginal septum / vaginal aplasia = Congenital cervical atresia > Symptoms (stating ot puberty) Primary amenorrhea: cryptomenormhea (false amenorrhea) = Cydic’ lower abdominal pain associated with progressive lower ‘abdominal swelling (mainly hematacolpos ) = Pressure manifestations: as dysuria & retention of urine > Sions = Abdominal: tense cystic pelviatdominal sweling © Vaginalbluish bulging hymen Rectally: distended vagina (continuous with the abd. swelling) > complications Haematocolpos, haematometra, haematosalpinx. Later on spillage of blood Into peritoneal cavity may lead to adhesions and infertility >» Treatment "General anesthesia + catheterization = Surgical drainage (cruciate incision) after written consent eees (@ True amenorrhea > Hypotholomic (rare) ~ Frholich syndrome Laurance Moon Beidel syndrome = Kallman syndrome > Pituitary (rare) .....Levb-Lorain syndrome. > Ovarien, ‘Tumer syndrome, Androgen insensitivity syndrome > Urerine. ‘Mullerian agenesis. # Congenital syndromes % Frohlich Reduced GH RH leading to reduced height, central obesity No GnRH leading to amenorthea, genital hypoplasia, no 2” sexual charactors + Laurence Moon Biedl.....a8 Frohlich syndrome, but there is also associated: ~ Limi deformity (polydactly / syndacty) = Mental Retardation ~ Blindness (Retinitis pigmentosa) + Kallman syndrome:- ‘Amenorrhea (isolated GnRH deficiency) is associated with anosmia (due to the common embryological pathway withthe nasal olfactory bulbs) © Levi-Lorain syndrome: Reduced GH + reduced gonadotrophins -» dwarfism + amenorrhea # Turner syndrome (10% of abortions; 1/2500 live births) 4 Clinical picture | = Genotype: 45 chromosomes (45x) ie. no Barr body. OR sometimes mosaic (45x0 ~ 46xx) oF (4x0 ~ 46xy). If mosaic she may be tall get menses: = get pregnant / but finally she wil have premature ovarian failure = Phenotype Short < 150 om, webbed neck, cubitus vulgus (wide carrying angle) Shield chest (widely spaced nipples & underdeveloped breasts) Coarctation of aorta, cardiac & renal abnormalities Hearing loss, hypothyroidism, liver dysfunction ~ Suspected in neonate by: lymphedema of dorsum of hands & feet ‘Short fourth metacarpal = External genitalia — infantile = Intomal genitalia streak ovaries (brous bands + no fllicles) estrogen + 1 FSH (hypergonadotrophic hypogonadism) ‘+ Cyclic estrogen and progesterone to ~ Stimulate breast, menstruation, prevents osteoporosis /coronary disease = Not given before 73 yrs (bone age) to avoid premature closure of epiphysis = Recombinant growth hormone can be added to increase height (+ Bem) 2- Gonadectomy is done only in mosaie types with Y-chromosome ~ As risk of malignancy 1s 25% (gonadoblastoma by 25 years)