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Amenorrhea

Amenorrhea. UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series. Objectives for Amenorrhea. Define amenorrhea and oligomenorrhea Explain the pathophysiology and identify the etiologies of amenorrhea and oligomenorrhea

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Amenorrhea

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  1. Amenorrhea UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series

  2. Objectives for Amenorrhea • Define amenorrhea and oligomenorrhea • Explain the pathophysiology and identify the etiologies of amenorrhea and oligomenorrhea • Describe the symptoms and physical examination findings of amenorrhea and oligomenorrhea • Discuss the steps in the evaluation and management of amenorrhea and oligomenorrhea • Describe the consequences of untreated amenorrhea and oligomenorrhea

  3. Definition • Amenorrhea – absence of menses • Primary amenorrhea – absence of menarche • Absence of menarche by age 14 without secondary sexual characteristics • Absence of menarche by age 16 with secondary sexual characteristics • Secondary amenorrhea – absence of menses in a previously menstruating woman • Absence of menses for > 6 months or duration of 3 menstrual cycles • Oligomenorrhea – reduction in frequency of menses • Cycle lengths > 35 days, but < 6 months

  4. Primary Amenorrhea: Etiology • Pregnancy • Thyroid disease • Hyperprolactinemia • Prolactinoma • Hypergonadotropic hypogonadism • Gonadal dysgenesis (i.e. Turner syndrome) • Premature ovarian failure • Hypogonadotropic hypogonadism • Constitutional delay of puberty • Congenital GnRH deficiency (Kallman syndrome) • Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa) • CNS tumor (i.e. Craniopharyngioma) • Normogonadotropic • Congenital (i.e. Mullerian agenesis, Androgen Insensitivity syndrome) • Outflow tract obstruction (i.e. Imperforate hymen, Transverse vaginal septum) • Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease)

  5. Primary Amenorrhea: Etiology • Most common etiologies: • Chromosomal abnormalities causing gonadal dysgenesis – 50% • Hypothalamic hypogonadism – 20% • Absence of the uterus, cervix, or vagina – 15% • Transverse vaginal septum or imperforate hymen – 5% • Pituitary disease – 5%

  6. Primary Amenorrhea: History

  7. Primary Amenorrhea: Physical Exam • Evaluation of pubertal development (height, weight) and growth chart • Breast development (Tanner staging) • Evaluation for features of Turner’s syndrome • Webbed neck, low hair line, shield chest, widely spaced nipples • Examine skin for hirsutism, acne, striae, increased pigmentation, and vitiligo • Pelvic exam • Clitoral size • Intactness of hymen • Depth of vagina • Presence of vaginal septum • Presence of cervix, uterus, and ovaries

  8. Tanner Stages Stage 1: Prepubertal, no palpable breast tissue or pubic hair. Stage 2: Development of breast bud; sparse, straight pubic hair. Stage 3: Enlargement of breast; pubic hair darker, coarser, and curlier. Stage 4: Areola and papilla project above the breast; pubic hair adult-like in appearance. Stage 5: Recession of areola to match contour of breast; pubic hair extends to thigh. Figure from: Roede, MJ, van Wieringen, JC. Growth diagrams 1980: Netherlands third nation-wide survey. TijdschrSocGezondheids 1985; 63:1. Reproduced with permission from the author.

  9. Primary Amenorrhea: Evaluation Secondary sexual characteristics present? No Yes Measure FSH Perform ultrasound of uterus FSH < 5 FSH > 20 Uterus absent or abnormal Uterus present or normal Hypogonadotropic hypogonadism Hypergonadotropic hypogonadism Karyotype analysis Outflow obstruction • Hypothalamic amenorrhea • Constitutional delay of puberty • Kallman syndrome • CNS tumor Karyotype analysis 46,XY 46,XX No Yes 46,XX 45,XO Müllerian agenesis Evaluate for 2° amenorrhea Androgen insensitivity syndrome Imperforate hymen Transverse vaginal septum Premature ovarian failure Turner’s syndrome • PCOS • Cushing’s

  10. Secondary Amenorrhea/Oligomenorrhea: Etiology • Pregnancy • Thyroid disease • Hyperprolactinemia • Prolactinoma • Breastfeeding, Breast stimulation • Medication (i.e. Antipsychotics, Antidepressants) • Hypergonadotropic hypogonadism • Postmenopausal ovarian failure • Premature ovarian failure • Hypogonadotropic hypogonadism • Functional hypothalamic amenorrhea (i.e. Anorexia or Bulimia nervosa) • CNS tumor (i.e. Craniopharyngioma) • Sheehan’s syndrome • Chronic illness • Normogonadotropic • Outflow tract obstruction (i.e. Asherman’s syndrome, Cervical stenosis) • Hyperandrogenic anovulation (i.e. PCOS, Cushing’s disease, CAH)

  11. Secondary Amenorrhea/Oligomenorrhea: Etiology • Most common etiologies: • Ovarian disease – 40% • Hypothalamic dysfunction – 35% • Pituitary disease – 19% • Uterine disease – 5% • Other – 1%

  12. Secondary Amenorrhea/Oligomenorrhea: History

  13. Secondary Amenorrhea/Oligomenorrhea: Physical Exam • General • Evaluation of height, weight, and BMI • Examine skin for hirsutism, acne, striae, acanthosis nigricans, thickness or thinness, and easy bruisability • Thyroid exam • Breast exam • Express for galactorrhea • Pelvic exam • Atrophy • Vaginal dryness

  14. Secondary Amenorrhea/Oligomenorrhea: Evaluation Negative urine pregnancy test Check TSH and prolactin Normal prolactin, Abnormal TSH Normal TSH, Abnormal prolactin Both normal Progestin challenge test Prolactin < 100 ng/mL Prolactin > 100 ng/mL Thyroid disease Withdrawal bleed No withdrawal bleed • Medication MRI to evaluate for prolactinoma Normogonadotropic hypogonadism Estrogen/progestin Challenge test Negative MRI Consider other causes • Hyperandrogenic anovulation • PCOS • Cushing’s No withdrawal bleed Withdrawal bleed • Medication Outflow obstruction Check FSH FSH > 20 IU/L Hypergonadotrpoic hypogonadism • Asherman’s • Cervical stenosis • Ovarian failure • Hypothalamic amenorrhea • Chronic illness MRI to evaluate for pituitary tumor Normal MRI Hypogonadotropic hypogonadism FSH < 5IU/L

  15. Secondary Amenorrhea/Oligomenorrhea: Evaluation • Progestin challenge test • Medroxyprogesterone acetate 10 mg daily for 10 days • IF withdrawal bleed occurs – Not outflow tract obstruction • IF no withdrawal bleed occurs – Estrogen/Progestin challenge test • Estrogen/Progestin challenge test • Oral conjugated estrogen 0.625 – 2.5 mg daily for 35 days • Medroxyprogesterone acetate 10 mg daily for 26-35 days • IF no withdrawal bleed occurs – Endometrial scarring • Hysterosalpingogram or Hysteroscopy to evaluate endometrial cavity

  16. Secondary Amenorrhea/Oligomenorrhea: Evaluation • Evaluation of hyperandrogenism • Symptoms: hirsutism, acne, alopecia, masculinization, and virilization • Differential diagnosis: • Adrenal disorders: Atypical congenital adrenal hyperplasia (CAH), Cushing’s syndrome, Adrenal neoplasm • Ovarian disorders: PCOS, Ovarian neoplasms • Lab: Testosterone, DHEA-S, 17α-hydroxyprogesterone

  17. Amenorrhea/Oligomenorrhea: Management • Treatment should be directed at… • Correcting the underlying pathology • Helping woman to achieve fertility (IF desired) • Preventing the complications of disease process • Consequences of untreated amenorrhea/oligomenorrhea: • Hypoestrogenism – Osteoporosis, Infertility • Hyperestrogenism – Heart disease, Stroke, Diabetes Mellitus, Breast cancer (controversial), Endometrial hyperplasia and Endometrial cancer

  18. Amenorrhea/Oligomenorrhea: Management *Causes of primary amenorrhea only

  19. Bottom Line Concepts • A thorough history and physical examination as well as laboratory testing can help narrow the diagnosis of amenorrhea. • In patients with primary amenorrhea, the presence or absence of sexual development should direct evaluation. • Constitutional delay of puberty is a diagnosis of exclusion. • The definitive method to identify hypothalamic-pituitary dysfunction is to measure FSH and prolactin levels. • If the patient has abnormal uterine development, a karyotype analysis should be performed to diagnose müllerian agenesis versus chromosomal abnormalities. • In a patient with secondary amenorrhea, pregnancy should be ruled out prior to further workup. • Treatment goals of amennorrhea and oligomenorrhea include prevention of complications such as osteoporosis, endometrial hyperplasia and heart disease; preservation of fertility; and in primary amenorrhea, progression of normal pubertal development.

  20. References and Resources • APGO Medical Student Educational Objectives, 9th edition, (2009), Educational Topic 43 (p92-93). • Beckman & Ling: Obstetrics and Gynecology, 6th edition, (2010), Charles RB Beckmann, Frank W Ling, Barabara M Barzansky, William NP Herbert, Douglas W Laube, Roger P Smith. Chapter 35 (p315-319). • Hacker & Moore: Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th edition (2009), Neville F Hacker, Joseph C Gambone, Calvin J Hobel. Chapter 32 (p355-363). • Master-Hunter T, Helman DL. Amenorrhea: evaluation and treatment. Am Fam Physician. 2006 Apr 15; 73(8): 1374-82.

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