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

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Presentation on theme: "Amenorrhea UNC School of Medicine Obstetrics and Gynecology Clerkship Case Based Seminar Series."— Presentation transcript:

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  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 Definition

4  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) Primary Amenorrhea: Etiology

5  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% Primary Amenorrhea: Etiology

6 Primary Amenorrhea: History FindingsAssociation Completion of stages of puberty? Development of axillary and pubic hair? Breast development? Ovarian or pituitary failure Chromosomal abnormality Family history of delayed or absent puberty?Familial disorder Constitutional delay of puberty Height relative to family members?Turner’s syndrome Symptoms of virilization?PCOS Ovarian or adrenal tumor Presence of Y chromosome Recent stress? Change in weight, diet, or exercise?Functional hypothalamic amenorrhea Medications (i.e. antidepressants, antipsychotics)?Hyperprolactinemia Galactorrhea?Hyperprolactinemia Headaches, visual field defects, fatigue, polyuria or polydipsia? Hypothalamic-pituitary disease

7  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 Primary Amenorrhea: Physical Exam

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. Tijdschr Soc Gezondheids 1985; 63:1. Reproduced with permission from the author.

9 Primary Amenorrhea: Evaluation Secondary sexual characteristics present? Measure FSH Perform ultrasound of uterus Karyotype analysis FSH > 20 Uterus absent or abnormal Uterus present or normal Turner’s syndrome Hypergonadotropic hypogonadism Hypogonadotropic hypogonadism 46,XX FSH < 5 46,XY Premature ovarian failure Karyotype analysis 46,XX45,XO Müllerian agenesis Androgen insensitivity syndrome Outflow obstruction Imperforate hymen Transverse vaginal septum Evaluate for 2° amenorrhea NoYes NoYes  Hypothalamic amenorrhea  Constitutional delay of puberty  Kallman syndrome  CNS tumor  PCOS  Cushing’s

10  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) Secondary Amenorrhea/Oligomenorrhea: Etiology

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

12 Secondary Amenorrhea/Oligomenorrhea: History FindingsAssociation Recent stress? Change in weight, diet, or exercise?Functional hypothalamic amenorrhea Development of acne, hirsutism, striae, central obesity, increased skin pigmentation or deepening voice? PCOS Cushing’s disease Ovarian or adrenal tumor Medications (i.e. antidepressants, antipsychotics)?Hyperprolactinemia Chronic illness?Functional hypothalamic amenorrhea Headaches, visual field defects, fatigue, polyuria or polydipsia? Hypothalamic-pituitary disease Symptoms of estrogen deficiency (hot flashes, vaginal dryness, decreased libido, or poor sleep)? Premature ovarian failure Postmenopausal ovarian failure Galactorrhea?Hyperprolactinemia History of obstetrical catastrophe, severe bleeding, D&C, endometritis, or other infection? Sheehan’s syndrome Asherman’s syndrome

13  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 Secondary Amenorrhea/Oligomenorrhea: Physical Exam

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

15  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 – 2.5 mg daily for 35 days  Medroxyprogesterone acetate 10 mg daily for days  IF no withdrawal bleed occurs – Endometrial scarring  Hysterosalpingogram or Hysteroscopy to evaluate endometrial cavity Secondary Amenorrhea/Oligomenorrhea: Evaluation

16  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 Secondary Amenorrhea/Oligomenorrhea: Evaluation Hormone Level Indication Testosterone< 200 ng/dLPCOS > 200 ng/dLEvaluate for adrenal or ovarian tumor DHEA-S< 700 ng/dLPCOS > 700 ng/dLEvaluate for adrenal or ovarian tumor 17α-hydroxyprogesterone> 4 ng/mLConsider ACTH stimulation test to diagnose CAH

17  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 Amenorrhea/Oligomenorrhea: Management

18 DiagnosisManagement Ovarian insufficiency  Premature ovarian failure  Postmenopausal ovarian failure Hormone replacement therapy (HRT) *Congenital anatomic lesionsSurgical correction *Presence of Y chromosome (i.e. AIS)Gonadectomy *Gonadal dysgenesis (i.e. Turner syndrome)Estrogen + progestin, growth hormone IVF (IF pregnancy desired) Hyperprolactinemia Dopamine agonist (Bromocriptine, Cabergoline) Functional hypothalamic amenorrheaIncrease caloric intake > energy expenditure Hypothalamic or pituitary dysfunction (non-reversible) OCP’s, pulsatile GnRH or exogenous gonadotropins CNS tumor  Craniopharyngioma  Prolactinoma Surgical resection Microadenoma (< 10mm) – Dopamine agonist Macroadenoma (>10mm) – Trans-sphenoidal resection PCOSOCP’s, weight loss, and metformin Asherman’s syndromeHysteroscopic lysis of adhesions *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, 9 th 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 (p ).  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 (p ).  Master-Hunter T, Helman DL. Amenorrhea: evaluation and treatment. Am Fam Physician Apr 15; 73(8):


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