gonadal hormone disorders for mbbs, bds, paramedical bachelor students.

1. Gonadal hormone
disorders
Binaya Tamang
lecturer
UCMS-TH

2. Hypothalamic-pituitary- gonadal axis
In Male: Sex steroid and inhibin together provide negative feedback
control of LH and FSH secretion respectively

3. Male reproductive abnormalities
üCan happen at any time
• Before birth
• In childhood
• In adulthood
üFor proper classification, they have been divided into 5 types.
1. Hypogonadotropic hypogonadism
2. Hypergonadotropic hypogonadism
3. Defects in androgen action
4. Impotence
5. Gynecomastia

4. 1.Hypogonadotropic hypogonadism
üDefects in hypothalamus or pituitary ( ↓ GnRH, LH & FSH)
üPrevent normal gonadal stimulation à↓ androgen: testosterone.
üCausative factors:
• Panhypopituitarism
• Hypothalamic syndrome/ structural defect
• GnRH def ( Kallmann’s syndrome)
• Hyperprolactinemia etc.

5. 2.Hypergonadotropic hypogonadism
üDue to primary defects in gonads
üPatient with testicular failure
• ↓ Testosteroneà as a result ↑ LH and ↑
FSH
üCauses are
• Acquired ( irradiation, mumps orchitis &
castration)
• Chromosomal defect: Klinefelter's
syndrome ( 47,XXY)
• Enzymatic defects in androgen biosynthesis
( like desmolase, 17 ⍺ hydroxylase, 3 β OH
SDH etc.)
• Testicular agenesis
• Seminiferous tubule disease.

6. 3.Defect in androgen action
üDefect in androgen action leads to testicular
feminization syndrome.
• Have female habitus
• Develop breast tissue
• However testes are present
üCause:
• defect in androgen receptorà so, no action
• Deficiency of 5 ⍺ reductase ( No formation
of DHTà NO action)
üMore androgen is directed towards more
estradiol formationà feminine character.
üCan also cause cryptorchidism (Undescended
testes in scrotum)

7. 4. Impotence
• Persistent INABILITY to develop or maintain PENILE ERECTION.
• Causes may be due to
• Psychological. ( most common diagnosis)
• Neuropathy
• Vascular disease
• Diabetes mellitus
• Hypertension
• Thyroid disorders
• Physicians go for above reasons, if no proper diagnosisà go for
testosterone, LH and TSH concentration .
• Sildenafil ( Viagra ) is used as an oral therapeutic agent.

8. 5.Gynecomastia
üBREAST IN MEN.
ü↑↑ estrogen/androgen ratio
ü3 distinct periods of life
• 1st transient gynecomastia: 60-90% of all
newborns because of high estrogen conc that
crosses placenta.
• 2nd during puberty ( 50-70% normal boys):it is
usually self limited
• May be due to low serum testosterone
• Low DHT
• High estro/andro ratio
• Last peak is seen in adult ( most freq 50-80 yrs
old)
§ Due to testicular failureà increased estro/andro
ratio
§ OR increased body fat, adipose tissue à ↑↑
aromatization of testosterone to estradiol.

10. Female reproductive
abnormalities
Before going,
Lets talk about CAH.

11. ADRENOGENITAL SYNDROME OR CONGENITAL
ADRENAL HYPERPLASIA (CAH)
• Characterized by ↑ in size of adrenal cortex
• Cause: congenital def. of enzymes for cortisol synthesis.
[21-hydroxylase def. is most common]
11
Partial or complete def. of enzyme req. for synthesis of GC & MC
↓
↓ed synthesis of cortisol
↓
Stimulates ACTH production
↓
Constant stimulation of adrenal cortex
↓
↑ in size of adrenal gland [Adrenal hyperplasia]
↓
↑ed secretion of Androgens à sexual abnormality.

12. 1. Female pseudo hermaphroditism
üGenetically female BUT
phenotypic characteristics are male
üFeatures like:
• 46xx karyotype ,
• Unclear genitaliaà clitoral
enlargement,
• virilization
üMOST common is Congenital
adrenal hyperplasia ( 21-
hydroxylase).
üOther deficient enzymes are: 11β
hydroxylase, 3βOH SD.

13. 2.Precocious puberty
üThe development of secondary sexual
characteristics < 8 yrs. in girls and < 9
yrs. for boys .
üManifested by:
• premature thelarche ( breast development)
• premature adrenarche ( Sexual hair
development)
• Clitoral enlargement in girls
• Phallic ( penis) enlargement in boys.
üClassified as TWO:
• GnRH dependent: aka CENTRAL
PRECOCIOUS PUBERTY. Early H-P-
G axis activation.
• GnRH independent: PSEUDO
PRECOCIOUS PUBERTY . e.g. CAH,
tumors of adrenal gland, ovaries.

14. 3.Amenorrhea: TWO types
ØAmenorrhea is the absence of a menstrual period in a woman of
reproductive age.
1) Primary amenorrhea : failure to start even after age of 16à never.
ümay be caused by
§ Vaginal aplasia
§ Congenital absence of uterus
§ Mullerian agenesis
§ Ovarian disorders ( PSOC, 17-hydroxylase def, Turner’s syndrome)
§ Adrenal disorders ( CAH)
§ Thyroid disorders ( hypo)
§ Axis disorders: kallmann’s syndrome

15. 2) Secondary Amenorrhea:
üprevious history of menstruation but absence for at least 6 months, or for
12 months with prior oligomenorrhea.
üOligomenorrhea: infrequent menstruation occurring less than 9 times per
year.( even > 35 days)
üMay be Caused by:
• Pregnancy/lactation: self limited.
• Uterine & Ovarian disorders ( Ashermann’s syndrome, PSOC, tumors)
• Adrenal disorders ( Cushing's syndrome, adrenocorticoid insufficiency)
• Thyroid disorders , Pituitary disorders ( Sheehan's syndrome)
• Hyperprolactinemiaà low LH & FSHà low estrogen/progesterone
ØPremature ovarian failure (loss of function of the ovaries < 40)à menopause

16. 4.Hirsutism
ØMale pattern hair growth in women in
are sensitive to androgen
ØIt is due to increased production of
androgens (male hormone)
ØCauses : vellus hair ( short, thin,
unpigmented) à thick hair
• Ovarian ( ovarian tumor, insulin resistance)
• Adrenal tumor and CAH
• Familial hirsutism
• Endocrine disorders ( PSOC,
hyperprolactinemia, acromegaly, Cushing )
• Idiopathic (increased sensitivity to
normal level of androgen)
• Drugs like minoxidil.

17. 5.virilization
üvirilization is associated with marked
increase in ovarian/adrenal androgen.
üAlso called as masculinization
• Hirsutism + other masculine
characters like
• Characterized by
• hirsutism
• Clitoral hypertrophy
• Deepening of voice
• frontotemporal balding
• Decreased in breast size ( body fat)
• Menstrual irregularities.
• Acne
• Bodybuilding: external steroid by female
• The most common cause of androgen
hypersecretion in women is PCOS.

18. Polycystic ovary syndrome (PCOS)
ØClinically defined as
hyperandrogenism with chronic
anovulation without underlying
disease of adrenal or pituitary
glands.
ØSigns and symptoms :
• Amenorrhea
• Heavy vaginal bleeding
• Hirsutism
• Acne
• Infertility
• Obesityà OVERWEIGHT
ØInsulin resistance, dyslipidemia,
glucose intolerance and type 2
diabetes are strongly associated
TWO of three criteria for PCOS
• Menstrual irregularity
• Clinical or biochemical androgen
level increased
• Multiple cyst in ovaries.

19. Lab diagnosis of male and female infertility
Normal values
Male infertility
Female infertility

20. 🙏THANK
YOU🌼😊