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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
Findings Association
Completion of stages of puberty? Development of Ovarian or pituitary failure
axillary and pubic hair? Breast development? Chromosomal abnormality
Family history of delayed or absent puberty? Familial disorder
Constitutional delay of puberty
Height relative to family members? Turner’s syndrome
Symptoms of virilization? PCOS
Ovarian or adrenal tumor
Presence of Y chromosome
Recent stress? Change in weight, diet, or exercise? Functional hypothalamic amenorrhea
Medications (i.e. antidepressants, antipsychotics)? Hyperprolactinemia
Galactorrhea? Hyperprolactinemia
Headaches, visual field defects, fatigue, polyuria or Hypothalamic-pituitary disease
polydipsia?
Primary Amenorrhea: Physical Exam
Pelvic exam
Clitoral size
Intactness of hymen
Depth of vagina
Presence of vaginal septum
Presence of cervix, uterus, and ovaries
Tanner Stages
Stage 1: Prepubertal, no
palpable breast tissue or
pubic hair.
Stage 2: Development of
breast bud; sparse,
straight pubic hair.
Stage 3: Enlargement of
breast; pubic hair darker,
coarser, and curlier.
Stage 4: Areola and papilla
project above the breast;
pubic hair adult-like in
appearance.
Stage 5: Recession of
areola to match contour
of breast; pubic hair
extends to thigh.
Figure from: Roede, MJ, van Wieringen, JC. Growth diagrams 1980: Netherlands third nation-wide survey.
Tijdschr Soc Gezondheids 1985; 63:1. Reproduced with permission from the author.
Primary Amenorrhea: Evaluation
No Yes
Findings Association
Recent stress? Change in weight, diet, or exercise? Functional hypothalamic amenorrhea
Development of acne, hirsutism, striae, central obesity, PCOS
increased skin pigmentation or deepening voice? Cushing’s disease
Ovarian or adrenal tumor
Medications (i.e. antidepressants, antipsychotics)? Hyperprolactinemia
Chronic illness? Functional hypothalamic amenorrhea
Headaches, visual field defects, fatigue, polyuria or Hypothalamic-pituitary disease
polydipsia?
Symptoms of estrogen deficiency (hot flashes, vaginal Premature ovarian failure
dryness, decreased libido, or poor sleep)? Postmenopausal ovarian failure
Galactorrhea? Hyperprolactinemia
History of obstetrical catastrophe, severe bleeding, Sheehan’s syndrome
D&C, endometritis, or other infection? Asherman’s syndrome
Secondary Amenorrhea/Oligomenorrhea:
Physical Exam
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:
Evaluation
Negative urine pregnancy test
Progestin challenge test Prolactin < 100 ng/mL Prolactin > 100 ng/mL
Thyroid disease
Normogonadotropic Estrogen/progestin
hypogonadism Challenge test Negative MRI
Hyperandrogenic Consider other
anovulation
causes
PCOS No withdrawal bleed Withdrawal bleed Medication
Cushing’s
Outflow obstruction Check FSH
Asherman’s FSH > 20 IU/L Hypergonadotrpoic
Cervical stenosis hypogonadism
Ovarian failure
Diagnosis Management
Ovarian insufficiency Hormone replacement therapy (HRT)
Premature ovarian failure
Postmenopausal ovarian failure
*Congenital anatomic lesions Surgical correction
*Presence of Y chromosome (i.e. AIS) Gonadectomy
*Gonadal dysgenesis (i.e. Turner syndrome) Estrogen + progestin, growth hormone
IVF (IF pregnancy desired)
Hyperprolactinemia Dopamine agonist (Bromocriptine, Cabergoline)
Functional hypothalamic amenorrhea Increase caloric intake > energy expenditure
Hypothalamic or pituitary dysfunction OCP’s, pulsatile GnRH or exogenous gonadotropins
(non-reversible)
CNS tumor Surgical resection
Craniopharyngioma Microadenoma (< 10mm) – Dopamine agonist
Prolactinoma Macroadenoma (>10mm) – Trans-sphenoidal resection
PCOS OCP’s, weight loss, and metformin
Asherman’s syndrome Hysteroscopic lysis of adhesions
*Causes of primary amenorrhea only
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 müllerian 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.
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).