Hypogonadism

Jason Ryan, MD, MPH

Hypogonadism
• Decreased activity of gonads (ovaries/testes)
• Primary: Disorder of gonads
• Secondary: Hypothalamus/pituitary disease
• Loss of LH/FSH

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Male Hypogonadism
• Primary hypogonadism
• Testosterone low
• LH/FSH increased
• Hypergonadotropic hypogonadism
• Secondary hypogonadism
• Testosterone low
• LH/FSH low (or normal)
• Hypogonadotropic hypogonadism

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Male Hypogonadism
Clinical Features

• Vary with on age of onset

• Pre-puberty
• Failure to undergo puberty normally
• Adult
• Decreased energy
• Decreased libido
• Infertility
• Loss of sexual hair, muscle mass, bones (untreated for years)
1° Male Hypogonadism
Select causes

• Klinefelter syndrome
• Myotonic dystrophy
• Swyer syndrome (gonadal dysgenesis)
• Mumps

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2° Male Hypogonadism
Select causes

• Pituitary tumors
• Pituitary apoplexy (hemorrhage into gland)
• Kallmann syndrome (GnRH deficiency/anosmia)

Wikipedia/Public Domain
Female Hypogonadism
• Primary hypogonadism
• Estrogen low
• LH/FSH increased
• Secondary hypogonadism
• Estrogen low
• LH/FSH low (or normal)
• Presents with amenorrhea

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Amenorrhea
• Primary amenorrhea
• Failure to menstruate by age 15
• Secondary amenorrhea
• Cessation of menses

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Primary Amenorrhea
• Pituitary disorders
• Hypopituitarism
• Kallmann syndrome (5:1 male ratio)
• Ovarian disorders
• Turner syndrome – most common cause
• PCOS in adolescence (androgen excess)
• Anatomic disorders
• Mullerian agenesis (absent vagina/uterus)
Mullerian agenesis
Mayer-Rokitansky-Küster-Hauser Syndrome

• Underdevelopment of Mullerian system

• Congenital absence of vagina
• Usually no cervix or uterus
• 1° amenorrhea
• Normal 2° sexual characteristics
• Breasts, pubic hair
• Ovaries functional
• Normal hormone levels
Secondary Amenorrhea
Selected Causes

• Pregnancy (anovulation)
• Menopause
• Hyperprolactinemia
• Thyroid disease
• Hyper and hypothyroid
• Anovulation
• Multiple mechanisms

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Secondary Amenorrhea
Selected Causes

• Corticosteroids/Cushing syndrome
• Cortisol suppresses GnRH
• Low LH/FSH
• Low estradiol
• Cirrhosis
• Disruption of hormone metabolism
• Variable levels of testosterone, estradiol, and prolactin
• Spironolactone
• Anti-androgen (disrupts estrogen/androgen balance)
• May stimulate progesterone receptors
Asherman Syndrome
• Uterine adhesions
• Adhesions/fibrosis of endometrium
• Infertility
• 2° amenorrhea
• 90% cases from uterine curettage
• Dilation and curettage (“D&C”)
• Cervix dilated, uterus scraped with a curette
• Damage to regenerative layer (basalis)
• Often done after pregnancy/miscarriage to remove tissue
Asherman Syndrome

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Primary Ovarian Insufficiency
Premature Ovarian Failure

• Hypergonadotropic hypogonadism
• Before 40 years of age
• Clinic features similar to menopause
• Hot flashes
• Vaginal dryness
• Elevated FSH
• Elevated LH
• Low estrogen
Secondary Amenorrhea
Key Diagnostic Tests
• hCG
• Prolactin
• TSH
• FSH
• High FSH seen in ovarian failure
• Brain MRI (exclude pituitary mass)
Functional Hypothalamic
Amenorrhea
• Common cause 2° amenorrhea
• Decrease GnRH secretion
• Low serum estradiol
• LH/FSH low or normal
• Risk factors
• Eating disorders
• Excessive exercise
• Weight loss
• Stress

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