Amenorrhea

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

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

9. Primary Amenorrhea: Evaluation

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

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

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 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 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, 17a-hydroxyprogesterone Secondary Amenorrhea/Oligomenorrhea: Evaluation

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. Amenorrhea/Oligomenorrhea: Management

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 m�llerian 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.