Gonadal failure

Question 1

What is gonadal failure

Answer 1

Hypogonadism is the failure of the ovaries or testis to produce sex steroids (oestrogen or testosterone). This can be from either gonadal failure (primary hypogonadism) or hypothalamic–pituitary failure (secondary hypogonadism).

The key difference between primary and secondary hypogonadism is whether LH/FSH levels are high (indicating an intact hypothalamic–pituitary axis) or low (damaged hypothalamic–pituitary axis).

Symptoms depend on whether the hypogonadism occurred before or after the onset of puberty

Question 2

What are the causes of gonadal failure?

Answer 2

Male
Primary Congenital - Klinefelter’s (XXY)
Primary Acquired - Renal Failure, Cirrhosis, Testicular Trauma/Surgery, Radio/Chemotherapy
Secondary Congenital – Kalman’s Syndrome (Hypothalamus does not release GNRH)
Secondary Acquired - Hyperprolactinaemia, Hypothalamic/Pituitary lesion

Female
Primary - Turners Syndrome (XO), Acquired Premature ovarian failure (Autoimmune)
Secondary - Hypothalamic/Pituitary disease, Hyperprolactinemia, Stress (Physical or physiological)

Question 3

What will you find in a history of Hypogonadism?

Answer 3

Symptoms Male:
Gynaecomastia
Diminished sex drive and erections
Loss of ejaculation
Low stamina
Loss of muscle bulk
Decreased secondary sexual hair
Osteoporosis 
If pre-pubertal failure – High pitched voice, No scrotal pigmentation, No pubic hair, No libido, Unable to achieve erection, Low Testicular volume (<5ml) and Penis length (<5cm)

Symptoms Female:
Fatigue
Amenorrhoea - Loss of periods
Infertility
Menopause like symptoms - hot flushes, sweats, mood, virginal dryness and painful intercourse occur in primary failure
If pre-pubertal failure - Will not start periods and may be short with impaired breast growth

Risk Factors:
Undescended testicles as an infant
Injury infection of the testilces
Chemotherapy/radiotherapy
Family history 

Specific Questions to ask:
Symptoms of underlying pituitary adenoma – Headache, bitemporal hemianopia, other pituitary hormones affected
Turners syndrome - Lymphedema, Cardiac or renal congenital anomalies, Neck webbing, Short growth pattern

Question 4

What will you find on examination of a patient with Hypogonadism?

Answer 4

Congenital anomalies and dysmorphic features may suggest a specific syndrome
Male – Reduction in size of testicles (compare to models or measure them), Micropenis, Stage puberty using Tanner Criteria
Female - Facial wrinkling, Breast involution, Reduction in body hair

Question 5

What investigations will you order in Hypogonadism

Answer 5

Bloods:
LH/FSH - Primary (LH/FSH raised, testosterone/oestrogen low) Secondary (Both low)
Special Tests:
If primary cause suspected order karyotyping tests
If secondary cause suspected order prolactin levels, MRI of pituitary fossa and hypothalamus
DEXA scan - At risk of osteoporosis

Question 6

What is the treatment of Hypogonadism

Answer 6

Male:
Primary Hypogonadism - Androgen replacement therapy will relieve symptoms and prevent osteoporosis, however infertility is irreversible in primary hypogonadism
Secondary Hypogonadism - Gonadotrophins or GnRH are used to induce fertility

Female:
Primary Hypogonadism - Oestrogen replacement therapy will relieve symptoms and prevent osteoporosis.
Progestogens added for women with an intact uterus to avoid endometrial hyperplasia and subsequent endometrial carcinoma. Oocyte donation is needed for fertility.
Secondary Hypogonadism - Gonadotrophins or GnRH are used to induce fertility