1. Reproduction-Related Disorders

2. Introduction
Reproductive endocrinology encompasses the hormones of the hypothalamic-pituitary-gonadal axis, as well as the adrenal glands.
These hormones are crucial for reproductive function and include:
Gonadotropin releasing hormone (GnRH),
Luteinizing hormone (LH),
Follicle-stimulating hormone (FSH), and
A multitude of sex steroids.
The sex steroids are responsible for the manifestation of primary and secondary sex characteristics, they are synthesized by the:
Ovaries,
Testes, and
Adrenal glands

3. Male Reproductive Biology
The function of the testes is to synthesize sperm and androgens where Sertoli and Leydig cells play key roles in this process.
For example, Sertoli cells in the seminiferous tubules of the testes have a crucial role in sperm maturation and secrete inhibin, a glycoprotein that inhibits the pituitary secretion of FSH.
Surrounding the seminiferous tubules are the interstitial Leydig cells, the primary site of androgen production.
The principal androgen in the human male is testosterone, which is required for:
Sexual differentiation, Spermatogenesis, and Promotion and maintenance of sexual maturity at puberty.

5. Summary of the endocrine control of the testis
Summary of the endocrine control of the testis. Dashed lines indicate inhibitory effects, and solid lines stimulatory effects. FSH, Follicle-stimulating hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone.
LH acts on Leydig cells to stimulate the conversion of cholesterol to pregnenolone.

6. Male Reproductive Abnormalities
A variety of abnormalities affect the male reproductive system before birth, in childhood, or in adulthood.
They can be divided into the categories of:
Hypogonadotropic hypogonadism,
Hypergonadotropic hypogonadism,
Defects in androgen action,
Erectile dysfunction, and
Gynecomastia.

7. Male Reproductive Abnormalities 1- Hypogonadotropic Hypogonadism
Male hypogonadism is a condition caused by decreased function of the testes, which can lead to retardation of sexual development if manifested early in life.
Occurs when defects in the hypothalamus or pituitary prevent normal gonadal stimulation. Causative factors include:
Congenital or acquired panhypopituitarism,
Hypothalamic syndromes,
GnRH deficiency,
Hyperprolactinemia,
Malnutrition or anorexia, and
Iatrogenic causes.

8. Male Reproductive Abnormalities 1- Hypogonadotropic Hypogonadism
All of these abnormalities are associated with decreased testosterone and gonadotropin concentrations
Kallmann syndrome, the most common form of hypogonadotropic hypogonadism, results from a deficiency of GnRH in the hypothalamus during embryonic development.
It is characterized by hypogonadism and anosmia (loss of the sense of smell) in male or female patients.
It is a congenital defect with several genetic causes that result in gonadotropic deficiency.

9. Male Reproductive Abnormalities 2- Hypergonadotropic Hypogonadism
Results rom a primary gonadal disorder.
Patients with primary testicular failure have increased conc. of LH and FSH and decreased concentrations of testosterone.
Causes for primary hypogonadism are categorized as:
Acquired causes (irradiation, castration, mumps orchitis, or cytotoxic drugs),
Chromosome defects (such as Klinefelter syndrome [47,XXY]),
Defective androgen synthesis (hydroxylase deficiency),
Testicular agenesis,
Seminiferous tubular disease, and
Other miscellaneous causes.
Aging is associated with gonadal failure, which leads to decreased testosterone secretion.

10. Male Reproductive Abnormalities 3- Defects in Androgen Action
The most common and severe defect in androgen action is androgen insensitivity syndrome (AIS), a disorder arising from mutations in the androgen receptor (AR) gene.
AIS is classified as complete (CAIS) or partial (PAIS), depending on the amount of residual receptor function.
Individuals with CAIS (formerly known as testicular feminization) have a male karyotype (46,XY) with female external genitalia and intraabdominal testes.
The circulating concentration of testosterone in these patients is greater than or equal to that of a healthy male, whereas LH concentrations are typically increased.

11. Male Reproductive Abnormalities 3- Defects in Androgen Action
Males with 5α-reductase deficiency (5-ARD) have reduced deficiency of the conversion of testosterone to the more potent dihydrotestosterone (DHT).
Because DHT leads to masculinization of external genitalia in utero, males with 5-ARD are born with ambiguous genitalia.
High ratios of the circulating concentrations of testosterone to DHT are indicative of 5-ARD.
In patients with cryptorchidism* or ambiguous genitalia, identification of abdominal gonads is essential for proper diagnosis and treatment.
a condition in which one or both of the testes fail to descend from the abdomen into the scrotum.
* one or both of the testes fail to descend from the abdomen into the scrotum.

12. Male Reproductive Abnormalities 3- Defects in Androgen Action
The presence of testicular tissue is detected by measurement of Leydig cell testosterone production after stimulation with human chorionic gonadotropin (hCG).
In addition, serum inhibin and plasma anti-Müllerian hormone may offer a noninvasive evaluation of seminiferous tubular integrity.
 Structurally, HCG is very similar to LH (Leutinizing Hormone). HCG acts like luteinizing hormone (LH). In males, LH stimulates the testes to produce testosterone. 
Expression during male fetal development prevents the mullerian ducts from developing into the uterus, resulting in development of the male reproductive tract.

13. Male Reproductive Abnormalities 4- Erectile Dysfunction
Erectile dysfunction (formerly referred to as impotence) is the persistent inability to develop or maintain a penile erection that is sufficient for intercourse and ejaculation in 50% or more of attempts.
Psychogenic erectile dysfunction is the most common diagnosis. Other causes include:
1.Vascular Disease
4.Hypertension
7.Drugs
10.Hypo-thyroidism
2.Neurologic Disease
5.Hypogonadism
8.Uremia
3.Diabetes Mellitus
6.Hyperthyroidism
9.Neoplasms

14. Male Reproductive Abnormalities 4- Erectile Dysfunction
If no obvious explanation for erectile dysfunction is found, measurement of morning serum testosterone, LH, and thyroid-stimulating hormone (TSH) concentrations has been suggested.
Elevated gonadotropin concentrations indicate primary hypogonadism.
Total and even free testosterone concentrations may be within reference intervals, yet still may be subnormal for a given patient if found in the presence of elevated LH or FSH.
LH for testosterone production

15. Male Reproductive Abnormalities 5- Gynecomastia
Gynecomastia, the benign growth of glandular breast tissue in men, is a common finding among males of varied ages.
Gynecomastia, which is associated with an increase in the estrogen/androgen ratio, is commonly associated with three distinct periods of life.

16. Male Reproductive Abnormalities 5- Gynecomastia
First, transient gynecomastia is found in 60% to 90% o all newborns because of high estrogen concentrations that cross the placenta.
The second peak occurs during puberty in 50% to 70% of healthy boys.
It is usually self-limited and may be due to a (1) low serum testosterone, (2) low DHT, or (3) high estrogen/androgen ratio.
The last peak is found in the adult population, most frequently among men aged 50 to 80 years.
Gynecomastia may be due to (1) testicular failure, resulting in an increased estrogen/androgen ratio, or to (2) increased body fat, resulting in increased peripheral aromatization of testosterone to E2.

17. Male Reproductive Abnormalities 5- Gynecomastia
Gynecomastia may also develop as the result of:
Iatrogenic causes,
Hyperthyroidism, or
Liver disease (impair hepatic degradation of estrogens).
In cases of striking gynecomastia in which history and physical examination point to no specific disorder, measurements of:
(1) hCG, (2) E2, (3) testosterone, and (4) LH concentrations are appropriate.
It is important to note that prolactin plays an important role in galactorrhea (milk production), but only an indirect role in gynecomastia (since it causes central hypogonadism and alters the androgen/estrogen ratio).
Liver injury may impair hepatic degradation of estrogens and increase levels of sex hormone–binding globulin that contribute to increased peripheral estrogens.