Amenorrhea

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

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

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

Clinical Presentation

History
milestones, development, diet, exercise, wt change drug use (antipsychotics, hormones, narcs, antiHTNs systemic disease (hypothyroidism, adrenal insuff., GH excess) past surgery, glactorrhea, hirsutism gyn/ob hx (hemorrhage, D&C, infection) genetic history

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)

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

DDx and Tx in Primary Amenorrhea: 2nd sex changes absent, cervix present
50% of patients primary ovarian disorders
Turners sd; pure gonadal dysgenesis; chromosomal mosaics; structural abnormalities of the sex chromosomes

CNS, hypothalamic, or pituitary failure

anatomic lesions; Kallmans sd; anorexia nervosa or bulimia; exercise induced; constitutional delay; hyperprolactinemia

Endocrinopathies (17 alpha hydroxylase deficiency)

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 17ahydroxylase 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

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

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

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

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

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