HORMON

FEMALE REPRODUCTIVE
SYSTEM
PRIMARY FUNCTIONS OF THE FEMALE
REPRODUCTIVE SYSTEM ARE:[1] PRODUCTION OF FEMALE
HORMONES.
[2] FORMATION OF THE OVUM.
[3] DEVELOPMENT OF THE
reproduction organs.
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FEMALE REPRODUCTIVE
ORGANS

FEMALE EXTERNAL GENITALIA

THE BREAST
DEVELOPMENT OF THE BREAST DUCTS
AND DEPOSITION OF FAT IN THE BREAST
TISSUE IS STIMULATED BY ESTROGEN.
DEVELOPMENT OF THE BREAST ALVEOLI IS
STIMULATED BY PROGESTRONE.
MILK PRODUCTION BY BREAST ALVEOLI IS
STIMULATED BY PROLACTIN.
MILK LET DOWN OR MILK - EJECTION IS
STIMULATED BY OXYTOCIN.

THE BREAST

OOGENESIS

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THE OOCYTE

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THE FEMALE HORMONES

HYPOTHALAMUS:- GONADOTROPIN
RELEASING HORMONE [GnRH].
PITUITARY:-LUTEINIZING HORMONE
[LH] FOLLICLE STIMULATING
HORMONE [FSH] PROLACTIN [PRL]
OVARY:DEVELOPING FOLLICLE:- ESTROGEN.
CORPUS LUTEUM:- PROGESTRONE.
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THE FEMALE MENSTRUAL CYCLES

ARE CYCLIC CHANGES IN THE
FEMALE
REPRODUCTIVE SYSTEM THAT ARE
CHARACTERIZED BY PERIODIC
VAGINAL BLEEDING.
THEY OCCUR AT THE SAME TIME AS: OVARIAN CYCLE
UTERINE CYCLE
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OVERIAN CYCLE
FOLLICULAR PHASE:- THE DEVELOPMENT
OF ONE PRIMARY FOLLICLE TO FORM A
MATURE FOLLICLE. {ESTROGEN}
OVULATION:- RUPTURE OF THE MATURE
FOLLICLE TO RELEASE THE OVUM.
LUTEAL PHASE:- FORMATION OF THE
CORPUS LUTEUM FROM THE RUPTURED
MATURE FOLLICLE. {PROGESTRONE}
DEATH OF THE CORPUS LUTEUM WILL
FORM A CORPUS ALBICANS.
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UTERINE CYCLE
MENSTRUATION:- BREAKDOWN OF THE
UTERINE ENDOMETRIUM AND VAGINAL
BLEEDING DUE TO LOW ESTROGEN
AND PROGESTRONE LEVELS.
PROLIFERATIVE PHASE:- GROWTH OF
THE UTERINE ENDOMETRIUM UNDER
ESTROGEN STIMULATION.
SECRETORY PHASE:- STIMULATION OF
THE UTERINE GLANDS SECRETION BY
PROGESTRONE.
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THE MENSTRUAL CYCLES

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Hormonal Feedback and the Regulation of the Female Reproduct

Estrogen syntesis
The most potent naturally occurring estrogen in
humans for both the Estrogen Receptor alpha- and
beta-mediated actions is 17beta-estradiol, followed by
estrone and estriol
Each estrogen contains a phenolic A ring with a
hydroxyl group at carbon 3 and a beta-OH or ketone in
position 17 of ring D
The phenolic A ring is the principal structural feature
responsible for selective, high-affinity binding to both
receptors
Synthesis of estrogen begins from the synthesis of
androstenedione from cholesterol
Androstenedione crosses the basal membrane into
surrounding granulosa cells, where its converted to
estrone or estradiol wither immediately or through
testosterone
The conversion is catalyzed by aromatase

Estrogens exert their effects by interaction with receptors

that are members of the super family of nuclear receptors
The two estrogen receptor (ER) genes are located on
separate chromosomes: ESR1 encodes ER-alpha and ESR2
encodes ER-beta
Both ERs are estrogen-dependent nuclear transcription
factors that have different tissue distributions and
transcriptional regulatory effects on target genes
Both ERs are ligand-activated transcription factors that
increase or decrease the transcription of target genes
After entering the cell by passive diffusion through the
plasma membrane, the hormone binds to an ER in the
nucleus
In the nucleus, the ER is present as an inactive monomer
bound to heat-shock proteins, and upon binding estrogen, a
change in ER confirmation dissociates the heat-shock
proteins and causes receptor dimerization, which increases
the affinity and the rate of receptor binding to DNA

Estrogen Effect
Estrogens are also responsible for
female secondary sex characteristics.
Deposition of fat in the breasts and
hips.
Increased water retention.
Affects calcium metabolism.
Stimulates of breast development.
Mediates female sexual behavior .

SERM
Selective Estrogen Receptor
Modulators (SERMs)
Compounds with tissue-selective actions
The goal of these drugs is to produce
beneficial estrogenic actions in certain
tissues (ex. Brain, bone, liver) during
postmenopausal hormone therapy
Tamoxifen, Raloxifen, Toremifine

Progesteron
In the reproductive tract, progesterone
decreases estrogen-driven endometrial
proliferation and leads to the development of a
secretory endometrium
The abrupt decline in progesterone at the end of
the cycle is the main determinant of the onset
of menstruation
Progesterone is very important for the
maintenance of pregnancy
It suppresses menstruation and uterine
contractility

Progesteron reseptor
Unlike the ER receptor, which requires a phenolic ring
for binding, the PR favors a non-phenolic ring structure
There is a single gene that encodes two isoforms of
the progesterone receptor (PR): PR-A and PR-B
Since the ligand-binding domains of the two PR
isoforms are identical, there is no difference in ligand
binding
However, the biological activities of PR-A and PR-B are
distinct and depend on the target gene in question
PR-B mediates the stimulatory activities of progesterone
PR-A strongly inhibits this action of PR-B

Upon binding progesterone, the heat-shock proteins

dissociate, and the receptors are phosphorylated and
subsequently form dimers (homo- and hetero-) that
bind with high selectivity to progesterone response
elements located on target genes

Anti progesteron
Anti-progestin, first discovered in 1981, is
mifepristone, used to terminate pregnancy
In the presence of progesterone, mifepristone
acts as a competitive receptor antagonist for both
progesterone receptors
When administered in the early stages of
pregnancy, mifepristone causes decidual
breakdown by blocking uterine progesterone
receptors, which leads to detachment of the
blastocyst, decreasing hCG production

Puberty
defined as transition period
between sexually immature child
to sexually mature, fertile adult
involves growth and maturation
of many tissues
timing has much individual
variability

OVARIAN CHANGE DURING

CHILHOOD
at birth, each ovary has ~500,000 follicles
no new follicles or eggs appear thereafter
some will partially develop during
childhood
will undergo atresia (insufficient LH and
FSH)
by puberty, each ovary has 83,000 follicles

Hormonal change at
puberty
in young children, LH and FSH levels
insufficient to initiate gonadal function
between 9-12 yrs., blood levels of LH,
FSH increase
amplitude of pulses increases,
especially during sleep
high levels of LH, FSH initiate gonadal
development

 GH secretion from pituitary also

increases
TSH (thyroid stimulating hormone)
secretion from pituitary increases in
both sexes:
increases metabolic rate
promotes tissue growth

Female Hormonal change

surge of LH release initiates 1st
ovarian cycle
usually not sufficient to cause
ovulation during 1st cycle
brain and endocrine systems mature
soon thereafter
estrogen levels in blood increase,
due to growing follicles

 estrogen induces secondary sex

characteristics:
growth of pelvis
deposit of subcutaneous fat
growth of internal reprod. organs,
external genitalia

androgen release by adrenal

glands increases > growth of
pubic hair, lowering of voice,
growth of bone, increased
secretion from sebaceous glands

Hypotalamic maturation
teory
Activation of reproductive system at
puberty is due to maturation of
hypothalamus. GnRH is driving force for
puberty
supporting evidence:
give immature monkey GnRH > will show
ovulatory cycles with estrogen, LH surges
tumors secreting GnRH can cause
precocious puberty

Tyming of puberty
trend toward earlier puberty
exists within Europe and USA
examination of lifestyle changes
may give clues regarding
mechanisms inducing onset

nutrion
Critical body weight must be attained
before activation of the reproductive
system.
earlier puberty due to improvement of
nutrition, living conditions, healthcare
evidence supporting hypothesis:
obese girls go through early menarche
malnutrition is associated with delayed
menarche
primary amenorrhea common in lean female
athletes

Precocious Puberty

Precocious puberty is sexual maturation that

begins before age 8 in a girl or before age 10 in a
boy.
In true precocious puberty, the sex glands
(ovaries or testes) mature and a child's outward
appearance becomes more adult. Pubic hair
grows, and the child's body shape changes.
In pseudoprecocious puberty, only the outward
appearance becomes more adult, while the sex
glands remain immature.
True precocious puberty is two to five times more
common in girls than in boys.

true precocious puberty

It is due to increased
production of pituitary
gonadotrophins.

In pseudoprecocious
puberty
It is of peripheral origin.
It is due to secretion of sex
hormones; (estrogen or androgen)
which is not dependent on pituitary
gonadotrophins as in case of
estrogenic or androgenic ovarian
tumors.

Incomplete Precociuos
Puberty
In this case only one pubertal change
as breast development is present
before the age of 8 years without the
presence of any other pubertal
changes and in absence of increased
estrogen production.
The other pubertal changes occur at
the normal age.

Causes
1. idiopathic:
In most cases of precocious puberty (90%) , no
cause is found.
For some unknown reason the hypothalamus
stimulates the pituitary gland to secrete its
gonadotrophic hormones.
There is normal menstruation and ovulation.
Pregnancy can occur at young age

2.Organic lesions of the brain:

The next common cause.
Organic lesions affecting the midbrain,
hypothalamus, pineal body, or pituitary gland
may lead to premature release of pituitary
gonadotrophins.
Examples include traumatic brain injury,
meningitis, encephalitis, brain abscess, brain
tumor as glioma, craniopharyngioma, and
hamartomas.

3. Adrenal causes:
(a) Hyperplasia, adenoma, or carcinoma of
suprarenal cortex.
Congenital adrenal hyperplasia and Cushing
syndrome lead to precocious puberty in the
male direction, i.e. heterosexual precocious
puberty;
(b) Estrogen secreting adrenal tumor which is
very rare.

4. Ovarian causes :
(a) Estrogen producing tumors as granulosa and
theca cell tumor;
(b) Androgen producing tumors as
androblastoma;
(c) Choriocarcinoma because it secretes human
chorionic gonadotrophin (HCG) which may
stimulate the ovaries to secrete estrogen;
(d) Dysgerminoma if it secretes HCG

5. Juvenile hypothyroidism:
Lack of thyroxine leads to increased production of thyroid
stimulating hormone and the secretion of pituitary
gonadotrophins may also be increased.
7. Drugs:
latrogenic may follow oral or local administration of estrogen.
A long course of estrogen cream used for treatment of
vulvovaginitis of children may lead to breast development or
withdrawal bleeding.

Symptom and Diagnosis

In both true precocious and
pseudoprecocious puberty, a boy
develops facial, under arm, and pubic
hair. His penis lengthens, and his
appearance becomes more masculine.
A girl may start to have menstrual
periods, especially if she has true
precocious puberty, or she may develop
breasts, pubic hair, and under arm hair.
In boys and girls, body odor changes,
and acne may appear.

 Diagnostic tests include measuring blood

hormone levels and taking x-rays of the
hand and wrist to estimate bone maturity.
Ultrasound examination of the pelvis and
adrenal glands and computed tomography
(CT) or magnetic resonance imaging (MRI)
of the brain are performed to see whether
tumors have developed in the adrenal
glands, hypothalamus, or pituitary gland.

Delayed Puberty
Secondary Sexual Characters
do not
develop by the age of 14 y
or
no menstruation till age of 16y

Delayed Puberty
It is either :
* Delayed onset: Breast bud does
not appear till 13 years or menarche
does not occur till 16 years .
or
* Delayed progreession :
Menarche does not occur within 5
years after breast bud .

Etiology
1 - Constitutional
with have family
history , short stature & normal fertility .
2 - Hypergonadotropic hypogonadism
3 - Hypogonadtropic hypogonadism =
hypothalamic & pituitary causes of
prymary amenorrhea, Anorexia nervosa .

 4 - Normogonadtropic hypogonadism
= end organ defects = uterine
causes (Mullerian agenesis and testicular
feminization syndrome), imperforate
hymen (c/o = delayed menarche + normal
other aspects of puberty).
5 - General causes of amenorrhea
(endocrinal or non-endocrinal especially
malnutrition) if occurred before puberty
&GH & steroid synthesis defects .

Diagnosis
History :
1 - Family history , nutritional history , any
systemic diseases (e.g. history of endocrinal
disturbance).
2 - Clinical picture of space occupying lesion
in the ovary , adrenal, pituitary &
hypothalamus.
3 - Periodic pain and have secondary sexual
characteristics in imperforate hymen .

Examination :
(A) Body measurement for causes of
amenorrhea + or weight, short or tall
stature , proportions (upper / lower
segment ratio & arm span / height ratio).
(B) Tanner staging of breast, pubic &
axillary hair if present.
(C) Clinical picture of Turner , Mullerian
agenesis & imperforate hymen .
(D) Neurological examination for,visual
field & other cranial nerve lesions .

 1 - FSH & LH assay important to

differentiate level of the lesion &
progesterone assay in 17 OH
deficiency .
2 - Chromosomal study if short
stature or hypergonadotropic type .
3 - Radiological bone age study &
radiologic study for pituitary adenoma

Treatment
* it treatable : Norethistrone acetate
5 mg twice daily for 21 d
* Patient with Y chromosome cell
line : Gonadectomy + hormone
replacement therapy