Male Hypogonadism

Review of Testosterone – Male Hypogonadism is due to abnormal testosterone secretion or action.

Synthesis – in Leydig cells of testes from cholesterol, stimulated by LH surface receptors

pituitary LH secretion stimulated by GnRH, inhibited by prolactin; testosterone exerts negative feedback on LH secretion

Secretion – into intertubular tissue fluid, diffuses into blood vessels and lymphatics

also secreted into seminiferous tubules where Ý testosterone is necessary for fertility

Transport in Blood:

44% bound to sex hormone binding globulin – strongly bound, NOT biologically inactive

Mechanism of Action – diffuses out of blood stream into interstitial fluid then into cell

binds hormone-receptor complex in nucleus Þ binds to DNA Þ influences mRNA production

Effects – fetal – stimulate differentiation of male internal and external genitalia

Post-puberty: Genital: growth and pigmentation of external genitalia, scrotal rugation, erections, spermatogenesis

Musculoskeletal: growth and maintenance of muscle and bone, fusion of epiphyses of long bones

Hair: growth of coarse, dark hairs on face and body, male pattern baldness (temples and crown)

Libido: Ý libido and aggressiveness; Fat: ß fat over hips, face, and chest; Voice: growth of vocal cordsÞ deepens voice

Male hypogonadism – abnormal testosterone secretion or action

Symptoms/Signs – fetal: ambiguous or female external genitalia; no female internal genitalia (testicle still makes MIF)

HYPOGONADISM	PRIOR TO PUBERTY	AFTER PUBERTY
Genital	Small testes, penis, and prostate, absence of scrotal pigmentation and poor rugation	Small, soft testes; prostate smaller than average, infertility
Musculoskeletal	ß muscle mass, delayed bone age, osteroporosis, eunuchoid proportions (long arms and legs because delayed closure of epiphysial growth plates)	ß strength and muscle mass; osteoporosis, Normal skeletal proportions
Hair	Female esutcheon (abdominal pubic hair in a trangular "female" pattern), absence of dark coarse hairs on face and body and male pattern baldness	ß growth of facial, pubic, and axillary hair. Normal pattern, no male pattern baldness
Libido	Decreased	Decreased libido and aggressiveness,
Voice	High-pitched	Normal
Fat	Prepubertal fat distribution over hips, face, chest	Normal
Fertility	Infertility	Impotence
Breasts	Gynecomastia (abnormalÝ breast tissue)	Gynecomastia
Skin		Crow’s feet (wrinkles lateral to eyes)

Etiologies – can be pathology in testes (Primary), pituitary (Secondary), or hypothalamus (Tertiary)

secondary and tertiary result in inadequate testicular stimulation by LH and FSH (mainly LH)

(1) Primary (testicular) Hypogonadism ("Hypergonadotrophic hypogonadism") – Ý LH and Ý FSH

Klinefelter’s Syndrome – extra X chromosome (47, XXY) due to X chromosome nondisjunction (during meiosis 1 or 2 in parent or first post-zygotic mitosis). Incidence Ý with increasing maternal age

Clinical Manifestation – eunochoid body habitus, gynecomastia, small firm testes, no sperm production

Histology – presence of Barr body (inactivation of extra X chromosome)

Autoimmune – anti-sperm antibodies Þ infertility, anti-Leydig cell antibodies Þ ß ß testosterone (associated with Addison’s)

Testicular resistance to LH – Leydig cells do not respond to testosterone (lack of LH receptor or receptor response)

Inherited enzymatic defect of testosterone synthesis

(2) Secondary (pituitary) Hypogonadism ("hypogonadotrophic hypogonadism") –no Ý LH despite ß testosterone

Destruction of pituitary – any disease process that destroys all or part of pituitary (tumor, hemochromatosis)

"Fertile eunuch" syndrome – rare congenital LH deficiency with findings of perpubertal hypogonadism

Aging – decline in gonadal function with aging; aging and LH deficiency have unclear mechanisms

(3) Tertiary (hypothalamic) hypogonadism ("hypogonadotrophic hypogonadism")

Kallman’s syndrome – absent hypothalamic GnRH-secreting neurons (no embryonic migration from olfactory bulb)

Findings: Anosmia (ß or absent sense of smell) Cause: no neural cell adhesion molecule

Disease of hypothalamus – destroys part or all of hypothalamus (tumor, sarcoidosis)

Suppression of GnRH secretion – systemic illness (acute or chronic) or prolactin-secreting pituitary tumors

(4) Androgen resistance syndromes – no response by target tissue

Testicular feminization–genetic males without androgen receptors Þ female external genitalia, no internal genitalia

grow breasts at puberty but no axillary or pubic hair; associated with Ý testosterone, Ý LH, and Ý FSH

5a reductase deficiency – deficiency in enzyme that converts testosterone into dihyrotestosterone

female-to-male switch – no male external genitalia before puberty; at puberty, testosteroneÞ male development

Treatment – testosterone replacement (IM, transdermal, or oral); Human chorionic Gonadotropin (mimics LH)