Definitions and Epidemiology

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

Definitions and Epidemiology

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

Clinical Presentation
y History
y milestones, development, diet, exercise, wt change y drug use (antipsychotics, hormones, narcs, antiy y y y

HTN s systemic disease (hypothyroidism, adrenal insuff., GH excess) past surgery, glactorrhea, hirsutism gyn/ob hx (hemorrhage, D&C, infection) genetic history

Clinical Presentation
y Physical y ht, wt, vitals y signs of thyroid dz (protuberant eyes, enlarged gland, puffy face, heat/cold intolerance) y secondary sex changes
y

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

y decreased breast size or vaginal dryness indication

decreasing estrogen exposure (or increasing androgens) y presence of a cervix (confirms presence of a uterus)

Etiology
y Primary amenorrhea

cause y Anorexia nervosa is the most common cause of amenorrhea overall in teens y Secondary amenorrhea y pregnancy is most common cause y 49-62% have hypothalamic disorders, including PCO y 7-16% have pituitary disorders y 10% have ovarian disorders y 7% have Ashermans syndrome

y gonadal failure is most common cause y uterovaginal agenesis is second most common

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

DDx and Tx in Primary Amenorrhea: 2nd sex changes absent, cervix present
y Work up includes measuring FSH
y if >40 and less than 30y/o

do karyotype y if Y chromosome exists, excise gonads y if 46XX, r/o 17a-hydroxylase deficiency y replace estrogen/progesterone, and if 17a-hydroxylase deficient, replace steroids also y if low, then a problem with the CNS, hypothalamic, or pituitary exists y measure serum prolactin y consider CT y no karyotype needed (all are 46XX) y replace estrogen/progesterone y consider GH y fertility requires assistance
y

DDx and Tx in Primary Amenorrhea: 2nd sex changes present, cervix present
y May present w/ primary or secondary amenorrhea y 1/3 of pts with primary amenorrhea have breasts and a uterus, 1/4 y

y y

of these have hyperprolactinemia CNS or hypothalamic causes y anatomic lesions (can appear with or without secondary sex changes y drugs affecting prolactin levels (stimulators and inhibitors) y stress, exercise, and eating disorders y PCOS y functional hypothalamic amenorrhea Pituitary causes Ovarian causes (elevated gonadotropin and low estrogen) y 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

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

DDx and Tx in Primary Amenorrhea: 2nd sex changes present, cervix absent
y androgen insensitivity (testicular feminization sd) y mullerian anomalies or agenesis y work up y karyotype and testosterone level y if nl body hair and female testosterone levels, uterine agenesis is present and pt is sterile
y y y

karyotype is to r/o male pseudohermaphrodism IVP should be done to r/o renal anomalies may need reconstructive surgery

y pts with AI are usually raised as girls (XY) y remove gonads after breast development and epiphyseal closure y replace estrogen

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

Secondary Amenorrhea
y Differential
y similar to that of primary amenorrhea with cervix and

secondary sex changes present y Work up y r/o pregnancy y r/o hyperprolactinemia y if prolactin level elevated, evaluate thyroid function y measure FSH and LH y measure 17a-hydroxylase progesterone and progesterone y do a progesterone challenge test y Treatment y dopamine agonist therapy y combination OCP therapy y estrogen replacement