Updated: 9/14/2018

Secondary Amenorrhea

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  • A 22-year-old female presents with increased hair growth. She reports having to shave frequently above the lip, chin, chest, and lower back. She also states not having her menses over a period of four months. Prior to this, she had a regular menses. The patient's weight is 168 lbs (76.2 kg) and height 5 feet and 1 inch (154.9 cm). On physical examination, there is increased hair above the lip and chin area. There is also acne on the cheeks and forehead. Hyperpigmented plaques of the skin are found in the back of the neck. Bilateral enlarged ovaries are palpated on pelvic examination. β-hCG is negative and LH:FSH is 3. (Polycystic ovarian syndrome)
Introduction
  • Absence of menses > 3 months in those with regular menses or absence of menses > 6 months in those with irregular menses
  • Etiology
    • pregnancy (most common)
    • hypothalamic dysfunction
      • e.g., functional hypothalamic amenorrhea, benign or malignant hypothalamic tumors, and systemic illness
        • functional hypothalamic amenorrhea
          • also known as functional hypothalamic GnRH deficiency
            • excludes pathological disease
          • risk factors
            • eating disorders, excessive exercise, and stress
        • hypothalamic tumors include
          • craniopharyngiomas
        • infiltrative disease affecting the hypothalamus include
          • Langerhans cell histiocytosis and sarcoidosis
    • pituitary dysfunction
      • e.g., prolactin-secreting pituitary adenoma and pituitary infarct (Sheehan syndrome)
    • thyroid disorder
      • e.g., hypothyroidism and severe hyperthyroidism
    • polycystic ovarian syndrome (most common reproductive disorder in women)
    • ovarian dysfunction
      • e.g., primary ovarian insufficiency  and ovarian malignancy 
    • uterine disorders
      • e.g., Asherman syndrome
Presentation
  • Symptoms and physical examination findings will be dependent on the etiology of secondary amenorrhea
    • e.g., patient with eating disorder (functional hypothalamic amenorrhea), hirsutism, or obesity (polycystic ovarian syndrome)
Evaluation
  • History and physical examination
    • history
      • e.g., eating disorder, excessive exercise, hyperandrogenism, visual defects, vaginal dryness, and hot flashes
    • physical examination
      • e.g., body mass index, acne, hirsutism, acanthosis nigricans, vitiligo, galactorrhea, and signs of estrogen deficiency on pelvic examination
  • β-hCG
    • best initial test
  • Follicle-stimulating hormone (FSH), prolactin (PRL), and thyroid-stimulating hormone (TSH)
    • order after ruling out pregnancy
    • assesses primary ovarian insufficiency, hyperprolactinemia, and thyroid abnormalities (e.g., severe hyperthyroidism and hypothyroidism)
  • Testosterone
    • should be ordered if there is evidence of hyperandrogenism
  • Progesterone challenge test
    • presence of withdrawal bleeding suggests
      • endogenous estrogen exposure
    • absence of bleeding suggests
      • hypoestrogenism or outflow tract obstruction
  • Estrogen-progesterone challenge test
    • presence of withdrawal bleeding suggests
      • inadequate estrogen
        • next step is ordering an FSH
    • absence of bleeding suggests
      • outflow tract obstruction or scarring of the endometrium
Differential Diagnosis
  • Pregnancy
  • Contraceptive use
  • Excessive exercise/physical stress 
  • Refer to introduction for causes of secondary amenorrhea
Treatment
  • Treatment depends on etiology of disease
    • as a rule of thumb, treat underlying pathology
    • examples include
      • functional hypothalamic amenorrhea
        • lifestyle modification
          • e.g., decreasing exercise and increasing caloric intake in patients with exercise excess
      • primary ovarian insufficiency
        • estrogen and progresterone therapy
      • Asherman syndrome
        • hysteroscopic lysis of adhesions
          • afterwards, place patient on estrogen therapy to stimulate regrowth of the endometrium
Prognosis, Prevention, and Complications
  • Complications
    • infertility
    • decreased bone density in patients with inadequate estrogen
 

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M2.GN.4867) A 23-year-old woman presents to her primary care physician due to amenorrhea. The patient states that historically she has her period once every three months but recently has not had it at all. Otherwise, she has no other complaints. The patient recently started college and is a varsity athlete for the track team. She works part time in a coffee shop and is doing well in school. The patient is not sexually active and does not drink alcohol, use illicit drugs, or smoke. She has no significant past medical history and occasionally takes ibuprofen for headaches. Her temperature is 99.5°F (37.5°C), blood pressure is 100/55 mmHg, pulse is 50/min, respirations are 10/min, and oxygen saturation is 98% on room air. On physical exam, you note a young, lean, muscular woman in no acute distress. Which of the following is the most likely long-term outcome in this patient? Review Topic | Tested Concept

QID: 109607
1

Endometrial cancer

8%

(4/49)

2

Infertility

10%

(5/49)

3

Osteoarthritis

0%

(0/49)

4

Osteoporosis

78%

(38/49)

5

Anorexia nervosa

4%

(2/49)

M2 D

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