2Amenorrhea Primary Secondary Absence of menses by age 16 with normal secondary sexual characteristicsAbsence of menses by age 14 without secondary sexual developmentSecondaryAbsence of menses for 6 months in a previously menstruating femaleThere is a 5% lifetime incidence for some form of amenorrhea.Physiologic causes of amenorrhea are:Prepubertal status, pregnancy, lactation, and menopause
3Events of Puberty Thelarche (breast development) Requires estrogenPubarche/adrenarche (pubic hair development)Requires androgensMenarcheRequires:GnRH from the hypothalamusFSH and LH from the pituitaryEstrogen and progesterone from the ovariesNormal outflow tract
8Primary Amenorrhea with Immature Sexual Characteristics Hypogonadism (gonadal failure)Gonadal dysgenesisIrradiationChemotherapyGalactosemiaNote: gonadotropins (FSH/LH) will be high, similar to menopauseIrradiation risk at >250 radsKallmann’s = insufficient pulsatile GnRH
10Primary Amenorrhea with Immature Sexual Characteristics HypogonadotropismHypothalamic dysfunctionKallmann syndromeAnorexia nervosaSpace-occupying lesion of CNSMarijuana usePituitary damage (surgery/radiation)Constitutional delayConstitutional delay: diagnosis of exclusion after negative workup including head CT/MRI. Bone age should be delayed as well.
12Primary AmenorrheaIs there normal development of secondary sexual characteristics?YESThinkPregnancyMullerian anomalyAndrogen insensitivityWith androgen insensitivity, there will typically be more breast development than pubic hair development.
13Primary Amenorrhea with Normal Secondary Characteristics Mullerian AnomaliesMullerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome)Imperforate hymenTransverse vaginal septumM-K-K-H is second most common cause of primary amenorrhea (1/4000)Mullerian aplasia -> nl breast devlpmt, body hair, blind vaginal pouchCheck for renal abnormalities (present in 34%), skeletal abnormalities (12%)
14Mayer-Rokitansky-Kuster-Hauser Syndrome (utero-vaginal agenesis) 15% of primary amenorrheaNormal secondary development & external female genitaliaNormal female range testosterone levelAbsent uterus and upper vagina & normal ovariesKaryotype 46-XX15-30% renal, skeletal and middle ear anomalies
16Androgen Insensitivity Normal breasts but no sexual hairNormal looking female external genitaliaAbsent uterus and upper vaginaKaryotype 46, XYMale range testosterone levelTreatment : gonadectomy after puberty + HRT
17Primary Amenorrhea Evaluation Pregnancy test Physical exam to determine presence of uterusFSHKaryotype
18Primary Amenorrhea Treatment Cyclic estrogen/progestin Remove gonadal streaks if XY or mosaicIncreased (52%) risk of gonadoblastomas, dysgerminomas, and yolk sac tumorsPulsatile GnRH for ovulation induction in select patientsSurgical resection of intrauterine, cervical, and vaginal adhesions/septa
26Secondary Amenorrhea Treatment goals Discovery and treatment of underlying disorderHormone replacementMenses every 1-3 monthsPregnancyOvulation inductionGnRH pumpFSH/LHPurpose for inducing menses at least every 3 months is to prevent endometrial hyperplasia and cancer
27Amenorrhea26 yo Gravida 0 with menarche at age 14 presents with one-year history of amenorrhea.
28Amenorrhea Sexually active, using condoms No recent change in weight, skin, hairOccasional heat intoleranceNo cyclic painNo gynecologic surgeryRegular menses (every days) prior to past year