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Chapter 21: Gonadal Function

By Marissa Grotzke

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes
Paired, ovoid organs
Dual functions

1. Production of sperm

2. Production of reproductive steroid hormones

Testosterone

In embryonic stage, aids in development & differentiation of


primordial gonads

After puberty, helps with sperm production & maintains


secondary sexual characteristics

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Functional Anatomy of the Male Reproductive Tract

Testes are located outside body, encased by a muscular sac.

Blood flow & contraction of dartos muscle regulate temperature of


testicles to 2C below core body temperature, which is vital to sperm
production.

Spermatic cord can retract testicles into inguinal canal when injury is
threatened.

Composed of 2 anatomic units:


Seminiferous tubules: contain germ & Sertoli cells (sperm
production)
Interstitium

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Physiology of the Testicles

Spermatogenesis
Spermatogonia: stem cells that form sperm
Spermatogonia undergo mitosis & miosis; haploid cells
transform to form mature sperm.
Mature sperm has head, body, & tail so it can swim.

Hormonogenesis
Testosterone: controlled by FSH & LH, which are produced
by gonadotrophs

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Physiology of the Testicles

Hormonal control of testicular function


Hypothalamus generates GnRH in pulsatile manner.
Testosterone is principal androgen hormone in blood.
Testosterone concentration fluctuates in a circadian fashion.

Cellular mechanism of testosterone action


Testosterone enters cell & converts to DHT.
DHT complexes with intracellular receptor protein, & this complex
binds to nuclear receptor, effecting protein synthesis & cell
growth.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Physiology of the Testicles

Physiologic actions of testosterone


Prenatal development: differentiation of male genital tract
Postnatal development: secondary sex hair, linear skeletal
growth, internal & external genitalia, muscles, voice deepens
Effect on spermatogenesis: paracrine effects (acting with
FSH) on seminiferous & Sertoli cells inducing spermatogenesis
Effect on secondary sexual effects: promotes growth of
various target tissues

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Disorders of Sexual Development and Testicular
Hypofunction

Hypergonadotropic hypogonadism
Klinefelters syndrome
Testicular feminization syndrome
5-alpha-reductase deficiency
Myotonic dystrophy
Testicular injury and infection
Sertoli-cell-only syndrome

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Disorders of Sexual Development and Testicular
Hypofunction

Hypogonadotropic hypogonadism
Kallmanns syndrome
Hyperprolactinemia
Age
Pituitary disease

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Diagnosis of Hypogonadism

Both clinical & biochemical features must be met.

Timing of sample must be considered (circadian rhythm).

Multiple estimation of free & bound levels done on different days

FSH and/or LH levels elevated in primary etiologies, but


inappropriately normal or low with secondary etiologies

Pituitary MRI should be done in secondary cases in young people.

Older people often have secondary or tertiary dysfunction.

Clinical signs & symptoms should be corroborated with low


testosterone levels.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Clinical diagnostic evaluation of male hypogonadism

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Testosterone Replacement Therapy

Parenteral testosterone
Intramuscular injection; most widely available & cost-effective

Transdermal testosterone therapy


Absorption from patch through skin; provides more physiologic levels

Testosterone gel
Gel applied to nongenital skin; risk of transmission to others

Buccal testosterone
Plastic tablet placed along gum line; local discomfort

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Testes (contd)


Monitoring Testosterone Replacement Therapy

Prostate-specific antigen (PSA), blood counts, & lipid levels


should be checked 36 months after initiation & yearly
thereafter.

Routine clinical evaluation for leg edema, sleep apnea, & prostate
enlargement

Pharmacologic use of testosterone may reduce sperm count.

If PSA is elevated, prostate evaluation with possible biopsy is


recommended.

Active prostate cancer is contraindication to testosterone


replacement.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary
Paired organs with dual functions

1. Gamete (ovum) production

2. Steroid hormone production

Primordial reproductive cells in female typically produce


solitary gamete.
Hormones from hypothalamus, pituitary, & ovaries
prepare uterus for implantation of embryo.
In absence of implantation, uterine lining is shed
(menses).
Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Functional Anatomy of the Ovary

Oval-shaped organs that lie in pelvic fossa

Positioned near fimbrial end of fallopian tubes

Adult ovary measures 25 cm in length, weighs 14 g.

Contain 24 million primordial follicles, present at birth

Follicular phase: All but 1 recruited follicles in a cycle atrophy.

Graafian follicle: Remaining follicle contains maturing ovum.

Luteal phase: Graafian follicle releases ovum in response to LH.

Luteinization: Graafian follicle develops into corpus luteum.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Hormonal Production by the Ovaries

Estrogen: promotes breast, uterine, & vaginal development

Progesterone: induces secretory activity of endometrial glands

Androgens: in excess, lead to hirsutism, loss of female


characteristics, development of male secondary sexual features

Others
Inhibins A & B inhibit FSH production; activin enhances FSH
secretion & induces steroidogenesis.
Folliculostatin, relaxin, follicle regulatory protein, oocyte
maturation factor, meiosis-inducing substance

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


The Menstrual Cycle

Starts on first day of menses (day 1)

Consists of two phases of parallel events occurring at ovaries &


endometrium

Follicular phase
Begins with onset of menses & ends on day of LH surge
A rise in FSH stimulates estrogen production.

Luteal phase
Starts with extrusion of ovum, about 36 hours after LH surge
Ends with onset of menses

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Hormonal Control of Ovulation

Central control of FSH & LH secretion resides in gonadotropinreleasing hormone (GnRH) pulse generator of arcuate nuclei &
medial preoptic nuclei of hypothalamus.

Positive & negative feedback responses exist among estrogen,


progesterone, LH, & FSH production.

A midcycle surge in LH production stimulates a series of events that


culminates in ovulation, with FSH levels falling thereafter.

Pubertal Development in the Female

Development of breast tissue (1st), pubic hair (2nd), menses (3rd);


measured by Tanner staging system

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Menstrual Cycle Abnormalities

Amenorrhea: absence of menses

Oligomenorrhea: infrequent or irregular menstrual bleeding

Hypogonadotropic hypogonadism
Deficiency of FSH & LH; can cause secondary amenorrhea

Hypergonadotropic hypogonadism
Ovarian failure with elevation of FSH concentrations

Polycystic ovary syndrome


Infertility, hirsutism, chronic anovulation, glucose intolerance,
hyperlipidemia or dyslipidemia, & hypertension

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Diagnostic approach to secondary amenorrhea

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Hirsutism

Abnormal, abundant, androgen-sensitive terminal hair growth

Cause is most commonly idiopathic (60%) or PCOS (35%).

Should only be considered in context of womans ethnic origin

Measured using Ferriman-Gallwey scale


Nine areas: lip, chin, sideburn region, neck, chest, abdomen,
upper & lower back, & thigh
Allots points on a scale of 14 based on hair thickness &
pigmentation
Score of >8 is consistent with diagnosis of hirsutism.

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins

The Ovary (contd)


Estrogen Replacement Therapy

Remains a contentious issue

Womens Health Initiative study found the following in 16,608


postmenopausal women who underwent estrogen replacement
therapy:
Increased incidence of invasive breast cancer & venous clot
formation
No benefit in cognitive decline or coronary artery disease
Reduction in bone loss, colon polyp formation, & menopausal
symptoms (hot flashes, vaginal dryness)

Remains a treatment option in select women after risk counseling

Copyright 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins