Human Reproductive System: Hormonal Control and Disorders

Male Gonadal Hormone

Testosterone Functions

• Embryologic male genital differentiation
• Maturation of the external genitals
• Skeletal muscle growth
• Deepening of the voice
• Epiphyseal cartilage growth during puberty
• Male hair growth and distribution
• Stimulation of sebaceous glands
• Male social behavior, libido

Testes

• Components:
  • Prostate gland
  • Urethra
  • Erectile tissue
  • Prepuce
  • Glans penis
  • Seminiferous tubules
  • Testis
  • Head of epididymis
  • Tail of epididymis
  • Urinary bladder
  • Ampulla
  • Seminal vesicle
  • Ejaculatory duct
  • Bulbourethral gland
  • Vas deferens
  • Epididymis
  • Scrotum
  • Leydig cells (interstitial cells)
  • Sertoli cells
  • Spermatogonium
  • Spermatids
  • Spermatozoa
  • Primary spermatocyte
  • Secondary spermatocyte

Male Sexual Function

Hormonal Control in the Male

• Integration of metabolic signals
• Higher centers:
  • Hypothalamus
    • GnRH
  • Pituitary
    • LH, FSH
  • Testes
    • Spermatogenesis
    • Leydig cell function
• Neuronal input
• Negative feedback (positive feedback)
  • Testosterone, inhibin

Puberty

• LH, FSH
• Testosterone

The 'Andropause'

Male Gonadal Dysfunction

• Causes:
  • Hypothalamic origin
  • Pituitary origin
  • Testicular origin
• Clinical Presentation in Adult Males:
  • Infertility
  • Erectile dysfunction
  • Loss of libido
  • Gynaecomastia
• Common problems:
  • Chronic renal failure
  • Orchitis
  • Drugs
  • Cancer of the testis

Male Hypogonadism

Clinical Features

• Depends on the age of onset
• Hypogonadism in the second to third month of fetal life results in ambiguous genitalia
• Hypogonadism before puberty results in failure of secondary sexual development
• Psychological effects:
  • Decreased aggression
  • Decreased activity
  • Decreased cognition
  • Decreased emotion
  • Decreased libido and impotence
• Defective spermatogenesis (low intratesticular testosterone)
• Decreased muscle mass with diminished muscle strength and endurance
• High-pitched voice due to the failure of thickening and maturation of the vocal cords
• Infantile genitalia

Causes

• Trauma (and surgery)
• Irradiation
• Drugs (alkylating agents, antiandrogens, spironolactone)
• Infection (viral, Syphilis, Leprosy, TB)
• Inflammation (autoimmunity)
• Infiltration (sarcoidosis, haemochromatosis)
• Chromosomal abnormalities
• Undescended testes and Varicocele
• Systemic illness, paraplegia, renal failure, and hepatic cirrhosis

Diagnosis

• Most important tests:
  • Serum testosterone
  • FSH
  • LH
  • SHBG
• Serum prolactin and estradiol levels may be useful
• Patterns:
  • Low testosterone with high gonadotrophins indicate gonadal dysfunction
  • Low testosterone with low gonadotrophins indicate pituitary/hypothalamic dysfunction
  • Hyperprolactinaemia may result in the suppression of testosterone secretion

Sexual Precocity

• Early sexual development before age 9 years caused by high androgens
• Virilisation without spermatogenesis
• Gonadotrophin-independent:
  • Leydig cell tumour or hyperplasia
  • CAH
  • Adrenal tumour
  • Androgen administration
• Gonadotrophin-dependent:
  • Idiopathic
  • HCG secreting tumours
  • CNS disorders
  • Tumours
  • Infections
  • Injuries

Test of Pituitary Function

• Intravenous injection of 100ug GnRH
• LH and FSH measured at 15, 30, 45, and 60 minutes post-injection
• Normal response:
  • Maximum LH of 2.5 times the basal level
  • Maximum FSH of 2 times the basal level

Gonadotrophin Releasing Hormone

• Stimulates secretion of LH and FSH

Klinefelter's Syndrome

Clinical Features

• Feminine body habitus
• Lack of body hair
• Gynaecomastia
• Long arms
• Sparse pubic hair
• Small testicles
• Tall stature, long legs

Causes

• Presence of an extra X chromosome, resulting in a 47XXY karyotype instead of the normal male karyotype (46XY)

Treatment

• Therapy consists of androgen replacement

Diagnosis

• Elevated levels of gonadotrophins
• Reduced serum testosterone
• Buccal Smear
• Karyotyping may be done on bone marrow, amniotic fluid, foetal cells, skin, solid tumours, or blood lymphocytes

Precocious Puberty

• Early development of secondary sexual characteristics and menstrual cycle
• Causes:
  • Idiopathic
  • Brain disorders (tumors and infections)
  • Ovarian (cysts and tumors)
• Adrenarche: age 9-10 years
• Thelarche (breast development)
• Menarche: by age 15 years (95% of girls)

Chromosomal Disorders

Turner's Syndrome

• Karyotype: 45 (XO)
• Incidence: 1:2500-3000
• Features:
  • Lymphoedema
  • Short stature
  • Hypogonadism
  • Low-set ears
  • Webbed neck
  • Skeletal abnormalities
  • Heart murmur

Testicular Feminisation (AIS)

• XY chromosome (male genotype), androgen insensitivity syndrome (AIS)
• Causes:
  • Various genetic mutations on the X chromosome
  • 1 in 20,000 live births
• Types:
  • Complete AIS: female phenotype
  • Incomplete AIS: varying degree of sexual ambiguity

Tests for Female Reproductive Function

• Gonadotrophins: LH and FSH
• Oestradiol
• Progesterone
• Prolactin
• Human Chorionic Gonadotrophins
• Androgens:
  • Testosterone
  • Androstenedione
• Dehydroepiandrosterone (DHEA and DHEAS)
• 17 hydroxyprogesterone
• Sex Hormone Binding Globulin (SHBG)
• Thyroid (T4, TSH); Cortisol; Growth Hormone

Polycystic Ovary Syndrome (PCOS)

Clinical Features

• Polycystic ovary syndrome
• Bitemporal hair loss
• Acanthosis nigricans
• Hirsutism
• Multiple cysts in the ovary
• Irregular menstrual cycle
• Acne
• Hirsutism
• Obesity

Diagnosis

• Clinical features
• Ultrasound scan
• Low SHBG
• High LH, low FSH
• High serum testosterone/FAI (free androgen index)
• High prolactin (will block the effect of LH & FSH on ovary)

Secondary Amenorrhoea (non-pregnant)

Primary Ovarian Failure

• Premature menopause
• Radiation/chemotherapy
• Post-infection

Secondary Ovarian Failure

• Hypothalamic/pituitary tumours
• Functional disorders
• Weight loss/anorexia nervosa
• Exercise
• Psychogenic
• General illness

Genital Tract Disorders

• Polycystic Ovary Syndrome

Ovarian Tumours

• Oestrogen or androgen-producing tumours (very rare)

Virilism and Hirsutism

• Virilism: female disorder involving development of male secondary sexual characteristics
• Hirsutism: common female complaint characterised by increased body hair with male pattern distribution
• Causes:
  • Androgen secreting tumour
  • Congenital Adrenal Hyperplasia (CAH)
  • Drugs
  • PCOS

Primary Amenorrhoea

Normogonadotrophic (normal LH and FSH)

• Anatomic defects
• Congenital adrenal hyperplasia (CAH)

Hypogonadotrophic (low LH and FSH)

• Hypopituitarism/hypothalamic disease
• Chronic illness
• Psychogenic
• Congenital syndromes (e.g., Prader Willi and Laurence Moon Biedl)

Hypergonadotrophic (raised LH and FSH)

• Turner's syndrome
• Gonadal irradiation/chemotherapy
• Androgen insensitivity syndrome 46 XY karyotype
• Congen

This quiz covers the hormonal control of male and female reproductive systems, including the Hypothalamus-Pituitary-Gonadals Axis, and female gonadal dysfunction disorders such as Polycystic Ovary Syndrome.