Amenorrhea

1. Amenorrhea Darren Farley, M.D. Department of Obstetrics and Gynecology UKSM-Wichita

2. Definitions and Epidemiology • Primary amenorrhea • absence of normal menstruation in a patient without previously established cycles • no periods by age 14 with no secondary sex changes • absence of menarche by age 16 regardless of secondary sex changes • no periods by 2 years after the start of secondary sex changes • < 0.1-2.5% of reproductive age women

3. Definitions and Epidemiology • Secondary amenorrhea • absence of menses for 3 cycle lengths in oligomenorrhea, or for 6 months after having regular menses • 1-5% of the population

4. Clinical Presentation • History • milestones, development, diet, exercise, wt change • drug use (antipsychotics, hormones, narcs, anti-HTN’s • systemic disease (hypothyroidism, adrenal insuff., GH excess) • past surgery, glactorrhea, hirsutism • gyn/ob hx (hemorrhage, D&C, infection) • genetic history

5. Clinical Presentation • Physical • ht, wt, vitals • signs of thyroid dz (protuberant eyes, enlarged gland, puffy face, heat/cold intolerance) • secondary sex changes • thelarche (breast devel): avg. age 10.8 yrs; indication of estrogen exposure • adrenarche (pubic/axillary hair development): avg. age 11 and indicates ovarian and adrenal androgen production and end organ response • decreased breast size or vaginal dryness indication decreasing estrogen exposure (or increasing androgens) • presence of a cervix (confirms presence of a uterus)

6. Etiology • Primary amenorrhea • gonadal failure is most common cause • uterovaginal agenesis is second most common cause • Anorexia nervosa is the most common cause of amenorrhea overall in teens • Secondary amenorrhea • pregnancy is most common cause • 49-62% have hypothalamic disorders, including PCO • 7-16% have pituitary disorders • 10% have ovarian disorders • 7% have Ashermans syndrome

7. DDx and Tx in Primary Amenorrhea:2nd sex changes absent, cervix present • 50% of patients • primary ovarian disorders • Turner’s sd; pure gonadal dysgenesis; chromosomal mosaics; structural abnormalities of the sex chromosomes • CNS, hypothalamic, or pituitary failure • anatomic lesions; Kallman’s sd; anorexia nervosa or bulimia; exercise induced; constitutional delay; hyperprolactinemia • Endocrinopathies (17 alpha hydroxylase deficiency)

8. DDx and Tx in Primary Amenorrhea:2nd sex changes absent, cervix present • Work up includes measuring FSH • if >40 and less than 30y/o • do karyotype • if Y chromosome exists, excise gonads • if 46XX, r/o 17a-hydroxylase deficiency • replace estrogen/progesterone, and if 17a-hydroxylase deficient, replace steroids also • if low, then a problem with the CNS, hypothalamic, or pituitary exists • measure serum prolactin • consider CT • no karyotype needed (all are 46XX) • replace estrogen/progesterone • consider GH • fertility requires assistance

9. DDx and Tx in Primary Amenorrhea:2nd sex changes present, cervix present • May present w/ primary or secondary amenorrhea • 1/3 of pts with primary amenorrhea have breasts and a uterus, 1/4 of these have hyperprolactinemia • CNS or hypothalamic causes • anatomic lesions (can appear with or without secondary sex changes • drugs affecting prolactin levels (stimulators and inhibitors) • stress, exercise, and eating disorders • PCOS • functional hypothalamic amenorrhea • Pituitary causes • Ovarian causes (elevated gonadotropin and low estrogen) • radiation and chemo; premature ovarian failure; ovarian resistance sd; PCOS; infection; vascular injury; cystetomy • Uterine causes (only group in this category who will show normal endocrine findings

10. DDx and Tx in Primary Amenorrhea:2nd sex changes present, cervix present • Work up • r/o pregnancy • r/o hyperprolactinemia • if prolactin level elevated, evaluate thyroid function • measure FSH and LH • measure 17a-hydroxylase progesterone and progesterone • do a progesterone challenge test • Treatment • dopamine agonist therapy • combination OCP therapy • estrogen replacement

11. DDx and Tx in Primary Amenorrhea:2nd sex changes present, cervix absent • androgen insensitivity (testicular feminization sd) • mullerian anomalies or agenesis • work up • karyotype and testosterone level • if nl body hair and female testosterone levels, uterine agenesis is present and pt is sterile • karyotype is to r/o male pseudohermaphrodism • IVP should be done to r/o renal anomalies • may need reconstructive surgery • pts with AI are usually raised as girls (XY) • remove gonads after breast development and epiphyseal closure • replace estrogen

12. DDx and Tx in Primary Amenorrhea:2nd sex changes absent, cervix absent • <1% of primary amenorrhea • pts are 46XY, but have abnormality in testosterone synthesis • mullerian inhibiting factor causes internal female organs to regress • DDx • 17a-hydroxylase deficiency • 17,20 desmolase deficiency • agonadism • Lab: elevated gonadotropins and low-normal female testosterone levels • Tx: remove testicles and replace estrogen; no need for progesterone

13. Secondary Amenorrhea • Differential • similar to that of primary amenorrhea with cervix and secondary sex changes present • Work up • r/o pregnancy • r/o hyperprolactinemia • if prolactin level elevated, evaluate thyroid function • measure FSH and LH • measure 17a-hydroxylase progesterone and progesterone • do a progesterone challenge test • Treatment • dopamine agonist therapy • combination OCP therapy • estrogen replacement