What are hypogonadism and amenorrhea?

Hypogonadism and Amenorrhea: Definitions, Types, and Clinical Implications

Hypogonadism refers to a condition of decreased production of sex hormones due to testicular or ovarian dysfunction, while amenorrhea is the absence of menstruation in women of reproductive age for three or more consecutive months. Both conditions can significantly impact quality of life, fertility, and long-term health outcomes including bone density and cardiovascular health.

Types of Hypogonadism

Female Hypogonadism

Female hypogonadism is characterized by decreased production of estrogen and progesterone, and can be classified into:

1. Primary Hypogonadism (Hypergonadotropic Hypogonadism)

   • Results from ovarian failure
   • Characterized by high FSH and LH levels
   • Causes include:
     • Ovarian dysgenesis (Turner syndrome)
     • Primary ovarian failure
     • Autoimmune oophoritis
     • Resistant ovary syndrome
     • Ovarian damage from radiation/chemotherapy 1
     • 46,XY disorders of sex development 2

2. Secondary Hypogonadism (Hypogonadotropic Hypogonadism)

   • Results from pituitary or hypothalamic dysfunction
   • Characterized by low or normal FSH and LH levels
   • Causes include:
     • Functional hypothalamic amenorrhea (stress, excessive exercise, low energy availability) 3
     • Hyperprolactinemia
     • Pituitary tumors or damage
     • Constitutional delay of puberty
     • Isolated hypogonadotropic hypogonadism 4

3. Normogonadotropic Hypogonadism

   • Normal gonadotropin levels but impaired ovarian function
   • Causes include:
     • Chronic diseases
     • Insulin resistance
     • Müllerian agenesis 2

Male Hypogonadism

Male hypogonadism involves decreased testosterone production and can be classified similarly:

1. Primary Hypogonadism

   • Testicular failure due to:
     • Cryptorchidism
     • Orchitis
     • Orchidectomy 5

2. Secondary Hypogonadism

   • Gonadotropin or LHRH deficiency
   • Pituitary-hypothalamic injury from tumors, trauma, or radiation 5

Types of Amenorrhea

1. Primary Amenorrhea

   • Absence of menarche by age 16 years or within 3 years of breast development 3
   • Evaluation should begin if:
     • No signs of puberty by age 13
     • No menarche by age 16 despite normal pubertal development
     • No menarche within 3 years after breast development began 3

2. Secondary Amenorrhea

   • Absence of menses for three or more consecutive months in women who previously had regular periods
   • Common causes include:
     • Pregnancy
     • Functional hypothalamic amenorrhea
     • Polycystic ovary syndrome
     • Hyperprolactinemia
     • Premature ovarian failure 3

Clinical Implications and Assessment

Health Consequences

Hypogonadism and amenorrhea can lead to:

• Decreased bone mineral density and increased fracture risk 1
• Increased cardiovascular risk 3
• Infertility
• Vaginal dryness and dyspareunia 1
• Psychological distress
• Impaired quality of life

Diagnostic Approach

Evaluation should include:

1. Hormonal Assessment

   • FSH, LH, estradiol/testosterone levels
   • Prolactin, TSH
   • AMH (anti-Müllerian hormone) for ovarian reserve 1

2. Imaging

   • Pelvic ultrasound to assess reproductive organs
   • MRI of hypothalamic-pituitary region if central cause suspected 6
   • Bone mineral density testing in cases of prolonged hypogonadism 1

3. Additional Testing

   • Karyotype analysis when chromosomal abnormalities are suspected
   • Assessment of energy availability, stress factors, and exercise habits 3

Management Approaches

Non-Pharmacological Approaches

• For functional hypothalamic amenorrhea:
  • Addressing underlying stress 3
  • Optimizing energy availability and nutrition 3
  • Modifying excessive exercise patterns 3
  • Ensuring adequate sleep and relaxation 3

Pharmacological Approaches

• Hormone Replacement Therapy:

  • Estrogen replacement (oral, micronized, or transdermal) with progesterone for women with a uterus 1
  • Testosterone replacement for men with hypogonadism 5
  • Note: Combined oral contraceptives may not be optimal for bone health in amenorrheic athletes due to first-pass effects on IGF-1 production 1

• Treatment of underlying causes:

  • Management of hyperprolactinemia
  • Treatment of thyroid disorders
  • Induction of puberty in adolescents with delayed puberty 5

Special Considerations

• Bone health monitoring is essential in prolonged hypogonadal states 1
• Fertility preservation options should be discussed with patients at risk of permanent gonadal failure 1
• Regular follow-up to assess treatment efficacy and monitor for complications

When to Refer

• Endocrinology/gynecology for delayed puberty, persistently abnormal hormone levels, or hypogonadism 1
• Reproductive endocrinology for fertility concerns
• Mental health professionals for associated psychological distress

Understanding the specific type and cause of hypogonadism or amenorrhea is crucial for appropriate management and prevention of long-term health consequences.