What are the causes of low estrogen levels in a 19-year-old female?

Causes of Low Estrogen in a 19-Year-Old Female

Low estrogen in a 19-year-old female is most commonly caused by functional hypothalamic amenorrhea (FHA) resulting from energy deficiency, excessive exercise, or psychological stress. 1 Other important causes include primary ovarian insufficiency, polycystic ovary syndrome, hyperprolactinemia, and thyroid dysfunction.

Primary Causes of Low Estrogen

1. Functional Hypothalamic Amenorrhea (FHA)

• Energy deficiency/Relative Energy Deficiency in Sport (RED-S)

  • Inadequate caloric intake relative to energy expenditure (EA <30 kcal/kg fat-free mass/day) 2
  • Rapid or significant fat mass reduction, even over a short 1-month period 2
  • Results in altered GnRH pulsatility and disrupted gonadotropin release 2

• Excessive exercise

  • Common in athletes, dancers, and those with high training volumes 2
  • Leads to suppression of hypothalamic-pituitary-gonadal axis 2

• Psychological stress

  • Chronic stress activates the hypothalamic-pituitary-adrenal axis 1
  • Increases cortisol levels which suppress reproductive hormones 2

2. Primary Ovarian Insufficiency

• Premature depletion of ovarian follicles 2
• Characterized by elevated FSH (>35 IU/L) and LH (>11 IU/L) 2
• May be caused by:
  • Genetic factors (Turner syndrome, fragile X premutation)
  • Autoimmune disorders
  • Previous cancer treatments (chemotherapy/radiation) 2
  • Radiation doses ≥10 Gy to ovaries can affect ovarian function in young women 2

3. Endocrine Disorders

• Thyroid dysfunction

  • Both hypothyroidism and hyperthyroidism can disrupt menstrual cycles 3
  • Present in 13.6% of adolescents with menstrual disorders 3

• Hyperprolactinemia

  • Elevated prolactin levels (>20 μg/L) suppress GnRH secretion 2
  • Can be caused by medications, pituitary adenomas, or stress 1

• Polycystic Ovary Syndrome (PCOS)

  • Despite being associated with hyperandrogenism, can present with low estrogen 2
  • Prevalence of 12.4% in adolescent populations with menstrual disorders 3
  • Characterized by LH/FSH ratio >2 2

4. Other Medical Causes

• Chronic illnesses

  • Inflammatory bowel disease, celiac disease, cystic fibrosis
  • Chronic kidney disease, liver disease

• Congenital abnormalities

  • Müllerian agenesis
  • Imperforate hymen

Diagnostic Approach

Initial Evaluation

1. Detailed menstrual history

   • Age of menarche, previous menstrual regularity
   • Duration of amenorrhea (>3 months should be investigated) 1

2. Assessment of energy availability factors

   • Weight changes, dietary habits, exercise patterns
   • BMI calculation (low BMI <18.5 kg/m²) 1

3. Laboratory testing

   • Pregnancy test
   • FSH, LH, estradiol
   • Prolactin, TSH
   • Consider testosterone if signs of hyperandrogenism 1

Additional Testing Based on Initial Results

• If elevated FSH/LH: Consider primary ovarian insufficiency, karyotype analysis 1
• If normal/low FSH/LH with normal prolactin and TSH: Consider FHA 1
• If normal/elevated LH with normal/low FSH: Consider PCOS 1
• If elevated prolactin: Consider pituitary imaging 1

Health Consequences of Low Estrogen

Bone Health

• Decreased bone mineral density and increased risk of stress fractures 2
• Peak bone mass occurs around age 19 in women, making this a critical period 2
• Estrogen inhibits osteoclast activity; when levels are low, bone resorption exceeds formation 2

Metabolic Effects

• Altered glucose metabolism and insulin sensitivity 2
• Changes in lipid profile
• Decreased metabolic rate 2

Cardiovascular Effects

• Endothelial dysfunction 1
• Increased risk of cardiovascular disease long-term 2

Psychological Effects

• Anxiety about normalcy 2
• Mood disturbances
• Body image concerns 1

Treatment Approach

For Functional Hypothalamic Amenorrhea

1. Address energy deficiency

   • Increase caloric intake by 20-30% over baseline
   • Target energy availability ≥45 kcal/kg fat-free mass/day
   • Aim for weight gain of approximately 0.5 kg every 7-10 days 1

2. Modify exercise patterns if excessive

   • Reduce training volume
   • Focus on weight-bearing activities that support bone health 1

3. Address psychological stressors

   • Consider cognitive behavioral therapy (CBT) 1
   • Stress management techniques

For Other Causes

• Thyroid dysfunction: Appropriate thyroid hormone replacement or suppression
• Hyperprolactinemia: Dopamine agonist therapy if indicated 1
• PCOS: Lifestyle modifications, cyclic progesterone therapy 1
• Primary ovarian insufficiency: Hormone replacement therapy 2

Bone Health Protection

• Ensure calcium intake of 1000-1300 mg/day
• Vitamin D supplementation to maintain levels between 50-75 nmol/L
• Consider transdermal estradiol (100 μg patch twice weekly) with cyclic oral progesterone (200 mg for 12 days each month) for bone protection 1

Common Pitfalls and Caveats

1. Assuming all amenorrhea in young women is physiological

   • Amenorrhea >3 months should always be investigated 1

2. Focusing only on weight without addressing energy availability

   • Even normal-weight individuals can have energy deficiency 2

3. Overlooking psychological factors

   • Stress and anxiety can independently cause hypothalamic suppression 1

4. Delaying treatment

   • Bone loss during this critical period may be irreversible 2
   • Early intervention is essential to prevent long-term health consequences

5. Missing underlying eating disorders

   • Screen for disordered eating behaviors which may be driving energy deficiency 1

Remember that low estrogen in a 19-year-old female requires prompt evaluation and treatment to prevent long-term health consequences, particularly related to bone health, which may be irreversible if not addressed early.