II. Definition

  1. No secondary sexual characteristics by 13 years old or
  2. No menstrual period by (failure to reach Menarche by):
    1. Fifteen years old or
    2. Three years after initial Breast development (Thelarche)

III. Causes

  1. See Hypogonadism
  2. Axis 1: Hypothalamus or Central
    1. Anovulation (10% of primary causes)
    2. Constitutional (6% of primary causes): Family History
    3. Gonadotropin deficiency such as Kallmann's Syndrome (Rare): Associated with Anosmia
  3. Axis 2: Pituitary
    1. Hyperprolactinemia (2% of primary causes)
    2. Pituitary Tumor (8% of primary causes)
      1. Pituitary Adenoma (hormone producing)
      2. Pituitary Null Cell Tumor (No hormone produced)
      3. Empty Sella Syndrome
      4. Pituitary Tuberculosis
      5. Pituitary Schistosomiasis
  4. Axis 3: Ovarian
    1. Polycystic Ovary Syndrome (10% of primary causes)
      1. Findings: Obesity, Hirsutism, and Acne Vulgaris
    2. Turner Syndrome and Mosaics (30% of primary causes)
      1. Findings: Short Stature, Web neck, and Shield Chest
      2. May present as Amenorrhea and Short Stature alone
    3. Genetic Male (10% of primary causes)
    4. Gonadal dysgenesis
  5. Axis 4: Uterus
    1. Mullerian Agenesis (20% of primary causes)
      1. Mayer-Rokitansky-Kuster-Hauser Syndrome
    2. Imperforate Hymen
    3. Transverse vaginal septum
    4. Complete androgen resistance

IV. History

V. Exam

VII. Imaging

  1. See Amenorrhea
  2. Pelvic Ultrasound

VIII. Evaluation: Protocol based on LH, FSH and Pelvic Ultrasound

  1. Obtain first-line testing as above
    1. Manage positive Pregnancy Test
    2. Manage Hypothyroidism
    3. Manage Hyperprolactinemia
  2. Uterus Present
    1. Low Serum FSH and Serum LH (Hypogonadotropic Hypogonadism)
      1. GnRH Deficient (rare)
      2. Functional Hypothalamic Amenorrhea
      3. Constitutional delay of Puberty
    2. Normal Serum FSH and Serum LH (Normogonadotropic Hypogonadism)
      1. Consider Obstruction to flow
        1. Imperforate Hymen
        2. Transverse vaginal septum
      2. Consider Hyperandrogenism (e.g. Hirsutism)
        1. Polycystic Ovary Syndrome
        2. Adrenal tumor
        3. Ovarian tumor
      3. Consider other causes
        1. See Secondary Amenorrhea
        2. Delayed Puberty
        3. New pituitary Tumor
    3. High Serum FSH and Serum LH (Hypergonadotropic Hypogonadism)
      1. Reflects Primary Ovarian Insufficiency
      2. Obtain Karyotype (previously Buccal Smear)
        1. Karyotype 46 XX
          1. Pituitary Defect
        2. Karyotype 45 XO
          1. Turner's Syndrome
  3. Uterus Absent
    1. Obtain Karyotype, Free Testosterone and Total Testosterone
    2. Female range Serum Testosterone and 46 XX
      1. Mullerian Agenesis
    3. Male range Serum Testosterone and 46 XY (genetic male)
      1. Androgen Insensitivity Syndrome (Male Pseudo-Hermaphrodite)
      2. 5a-Reductase Deficiency

IX. Evaluation: Protocol based on Growth and Development (Female Tanner Stage, Delayed Linear Growth, Uterus Presence)

  1. Obtain first-line testing as above
    1. Manage positive Pregnancy Test
    2. Manage Hypothyroidism
    3. Manage Hyperprolactinemia
  2. Abnormal Breast development and Female Tanner Stage
    1. Normal Height with low gonadotopins (FSH, LH <5 IU)
      1. See Hypogonadotropic Hypogonadism
      2. Obtain Karyotype (previously Buccal Smear)
        1. Karyotype normal
          1. GnRH Deficient (rare)
          2. Functional Hypothalamic Amenorrhea
          3. Constitutional delay of Puberty
        2. Karyotype abnormal
          1. Pure Gonadal dysgenesis
    2. Short Height and excess gonadotropins (FSH>20, LH>40)
      1. See Hypergonadotropic Hypogonadism
      2. Reflects Primary Ovarian Insufficiency
      3. Obtain Karyotype (previously Buccal Smear)
        1. Karyotype 46 XX
          1. Pituitary Defect
        2. Karyotype 45 XO
          1. Turner's Syndrome
  3. Normal Breast development and Female Tanner Stage
    1. See Normogonadotropic Hypogonadism
    2. Uterus Absent on Ultrasound
      1. Karyotype (previously Buccal Smear)
      2. Karyotype 46 XX
        1. Mullerian agenesis (Mullerian Dysgenesis)
        2. Serum Testosterone in normal female range
      3. Karyotype 46 XY (genetic male)
        1. Androgen insensitivity syndrome (Male Pseudo-Hermaphrodite)
        2. 5a-Reductase Deficiency
        3. Serum Testosterone in normal Male range
    3. Uterus Present on Ultrasound
      1. Consider obstruction to flow
        1. Imperforate Hymen
        2. Transverse vaginal septum
      2. Consider Hyperandrogenism (e.g. Hirsutism)
        1. Polycystic Ovary Syndrome
        2. Adrenal tumor
        3. Ovarian tumor
      3. Consider other causes
        1. See Secondary Amenorrhea
        2. Delayed Puberty
        3. New pituitary Tumor

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Ontology: Primary physiologic amenorrhea (C0232939)

Definition (NCI) Abnormally late or absent menarche in a female with normal secondary sexual characteristics.(NICHD)
Concepts Disease or Syndrome (T047)
ICD10 N91.0
SnomedCT 156035004, 8913004
Dutch primaire amenorroe, amenorroe; primair, primair; amenorroe, Primaire amenorroe
French Aménorrhée primaire, Aménorrhée primitive
German Amenorrhoe primaer, primaere Amenorrhoe, Primaere Amenorrhoe
Italian Amenorrea primaria
Portuguese Amenorreia primária
Spanish Amenorrea primaria, amenorrea fisiológica primaria (hallazgo), amenorrea fisiológica primaria, amenorrea primaria
Japanese 原発性無月経, 原発性無月経症, ゲンパツセイムゲッケイショウ, ゲンパツセイムゲッケイ
English primary amenorrhea, primary amenorrhea (diagnosis), Amenorrhoea primary, amenorrhea primary, Amenorrhea, primary, Primary amenorrhoea (finding), Primary Amenorrhea, Delayed Menarche, Primary physiologic amenorrhea, Primary amenorrhea, Primary amenorrhoea, Primary physiologic amenorrhoea, Primary physiologic amenorrhea (finding), Amenorrhea primary, primary; amenorrhea, amenorrhea; primary, primary amenorrhoea, Amenorrhea;primary, Amenorrhoea;primary
Czech Primární amenorea, Amenorea primární
Korean 원발성 무월경
Hungarian Primaer amenorrhoea, primaer amenorrhoea

Ontology: Late menarche (C0520930)

Concepts Physiologic Function (T039)
SnomedCT 83017007
English late menarche, Late menarche, Late menarche (finding)
Spanish menarca tardía (hallazgo), menarca tardía