ESTROGEN & PROGESTIN FOR V SEMESTER B.PHARM STUDENTS

1. ESTROGEN
&
PROGESTIN
FEMALE
SEX
HORMONE
By
Dr.S.KAMESHWARAN.,M.Pharm.,Ph.D.,
Associate Professor, Excel College of Pharmacy
Komarapalayam, Tamilnadu

2. MENSTURAL CYCLE

3. ESTROGENS
Female sex hormones.
ESTROGEN IS THE SUBSTANCE WHICH CAN INDUCE
ESTRUS IN SPAYED ANIMAL
 Natural estrogens are steroid hormones, while some
synthetic ones are non-steroidal.
 ESTROGEN =Greek
Oistros - Sexual desire, gen - "producer of".
 Like all steroid hormones, estrogens readily diffuse
across the cell membrane. Goes inside the cell, they
bind & activate estrogen receptors which in turn
modulate the expression of many genes.
 Estrogen levels vary through the menstrual cycle with
levels highest near the end of the follicular phase just
before ovulation.

4. NATURAL ESTROGENS:
Estradiol is the major estrogen secreted by the
ovary.
It is synthesized in the graffian follicle, corpus
luteum & placenta from cholesterol,
Estrediol is the most potent estrogen.
ESTREDIOL
↓ Oxidized in liver
ESTRONE
↓
ESTRIOL
Estrone (E1), Estradiol (E2) & Estriol (E3) all 3 are
found in blood

5. ESTRADIOL:
 It is the predominant estrogen during reproductive
years,
 It is the strongest with a potency of approximately
80 times than estriol.
 It is the most important estrogen in non-pregnant
females who are between the menarche (first
menstrual cycle) and menopause stages of life.
ESTRONE
 It is the predominant estrogen during menopause,
ESTRIOL
 It is the predominant estrogen during pregnancy.
 It is the most plentiful of the three estrogens
 It is also the weakest,

6. REGULATION OF SECRETION:
Amount of secretion of estrogen depending on
the phase of the cycle.
Secretion starts from GRAFIAN FOLICLE, under the
influence of FSH.
Blood level raises during follicular phase after
ovulation, Corpus luteum continues to secrete
estrogen till about 2 days before menstruation.
DURING PREGNENCY – placenta secrete large
quantities of estrogen 30mg /day, which reduced
after delivery.
IN POST MENOPUSAL WOMEN: very low amount
secretes.

7. SYNTHETIC ESTROGENS:
All are Synthetic estrogens
Natural estrogens are inactive, because of first pass
metabolism in liver therefore, synthetic estrogens are
prepared.
STEROIDAL:
ETHNYLESTRADIOL
MESTRANOL
TIBOLONE
NON-STEROIDAL:
DIETHYLSTILBESTEROL
HEXESTROL
DIENESTROL
All preparations have similar action.
Potencies differ from others due to the type of first
pass metabolism.

8. ACTIONS:
PUBERTAL CHANGES IN FEMALE
Growth of uterus, fallopian tube and vagina.
Vaginal epithelium gets thickened, stratified and
cornified.
Proliferation of endometrium in the pre ovulatory
phase, Progesterone brings secretory changes.
Increase rhythmic contraction of fallopian tubes and
uterus; induce watery alkaline secretion from the
cervix.
SECONDERY SEX CHARECTERS:
Growth of breasts.
Pubic and axillery hair.
Feminine body contours (STRUCTURE), behavior.
Acne

9. MECHANISM OF ACTION:
ESTROGEN
↓
BIND TO SPECIFIC NUCLEAR RECEPTOR
IN TARGET CELLS
↓
PROTIEN SYNTHESIS
↓
BIOLOICAL EFFECT

10. PHARMACOKINETICS:
Well absorbed orally & transdermally
Natural estrogens are inactive orally,
Natural estrogens are largely bound to protein
Estradiol, estriol, estrone are metabolized in liver
Excreted in urine & bile
ADR:
Suppression of libido
Gynaecomastia
Feminization
Irregular bleeding
Breast cancer
Gall stones

11. PROGESTINS
PROGESTIN = FAVPURING PREGNENCY
“THESE ARE THE SUBSTANCE WHICH CONVERT
THE ESTROGEN PRIMED ENDOMETRIUM TO
SECRETORY & MAINTAIN PREGNANCY IN
ANIMAL SPAYED AFTER CONCEPTION”
• Identified in 1929, but full therapeutic potential
find out after 1950
• After that large number of orally active
synthetic progestin's were developed.

12. NATURAL PROGESTIN:
It is a 21 carbon steroid, Derived from cholesterol
It is secreted from corpus luteum (10-20mg/day) during
the menstrual cycle by LH
Synthesis Declines few days before the next menstrual
cycle
If ovum gets fertilized and implants blastocytes
producing CHRONIC GONADOTROPIN, which sustains
corpus luteum in early pregnancy
In second trimester placenta secretes lot of estrogens
and progesterone
SYNTHETIC PROGESTINS:
It is highly active orally
Various synthetic progestin's are available nowadays
PROGESTERONEDERIVATIVES (contain 21 carbon)
19-NORTESTOSTERONE DERIVATIVES (contain 18
carbon)

13. PROGESTERONE DERIVATIVES:
MEDROXY PROGESTERONE ACETATE
MEGESTROL ACETATE
DYDROGESTRONE
HYDROXY PROGESTRONE CAPROATE
NOMEGESTROL ACETATE
19-NORTESTOSTERONE DERIVATIVES
OLDER DRUG: NEWER DRUGS:
NOR ETHINDRONE DESOGESTREL
LYNESTRENOL NORGESTIMATE
ALLYLESTRENOL GESTODENE
LEVONORGESTREL

14. ACTIONS:
• Mainly progesterone prepare the uterus for nidation
(implantation) & maintenance of pregnancy
UTERUS:
• Secretory changes in the estrogen primed
endometrium,
• Hyperemia (increase of blood flow)& tortuocity
(twist) of glands occurs and increases the secretion
• During pregnancy causes decidual changes
(characteristic of the endometrium of the pregnant
uterus) in endometrium, enlargement of stroma it
become spongy
• Decreases the sensitivity of myometrium to oxytocin

15. CERVIX:
Estrogen

Watery cervical secretion
Progestin
Viscid, scandy fluid
Which is
Hostile to sperm penitration
VAGINA:
Induce pregnancy like changes in vaginal
mucosa

16. BREAST:
• Proliferation of acini in the mammary gland
• Prepares breast for lactation
• After child birth  withdrawal of progestin
release of prolactin from pituitary  Milk secretion
CNS:
• During pregnancy  High concentration of
progesterone  induce sedation
BODY TEMPERATURE:
• Cause slight raise in temp (0.5oc)
RESPIRATION:
• At high dose – stimulate respiration during
pregnancy

17. MECHANISM OF ACTION:
 Only limited progestin receptor present in the body
 Mostly present in females, in Genital tract, Breast, CNS, Pituitary.
 Located in the nucleus of the target cell
PROGESTERONE

BINDS TO PROGESTIRONE RECEPTOR PRESENT ON THE
TARGET CELL

DIMERIZATION OF RECEPTOR

DIFFUSE IN TO NUCLEUS

BINDS TO PROGESTERONE RESPONSE ELEMENT OF TARGET
GENE

REGULATION OF TRANSCRIPTION

SPECIFIC PROTEIN SYNTHESIS

BIOLOGICAL ACTION

18. PHARMACOKINETICS:
 It is inactive orally
 But the synthetic progesterone are orally active
 Mostly injected (i.m) in oily solution
 Has short half life 5-7 minutes
 Metabolized in liver
 Excreted in urine
 Microionized formulation of progesterone administered in the form
of soft gelatin capsule
ADR:
 Breast enlargement
 Head ache
 Rise in body temperature
 Edema
 Acne
 Irregular bleeding

19. THANK U FINAL YRS