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
• lt 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-HTNs
• systemic disease (hypothyroidism, adrenal
  insuff., GH excess)
• past surgery, glactorrhea, hirsutism
• gyn/ob hx (hemorrhage, DC, 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 Amenorrhea2nd 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)

8
DDx and Tx in Primary Amenorrhea2nd sex changes
absent, cervix present

• Work up includes measuring FSH
• if gt40 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 Amenorrhea2nd 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 Amenorrhea2nd 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 Amenorrhea2nd 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 Amenorrhea2nd sex changes
absent, cervix absent

• lt1 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