female sex hormones oestrogen and progesterone

1. Female sex hormones
*Estrogens
*Progestins

2. Ovary- important gametogenic functions
- hormonal activity
Disturbances – most self limited
- caused by temporary alterations of stress centres,
emotions
- anovulatory cycles assoc. with eating disorders &
with severe exercise

3. • Organic causes are
1. pituitary prolactinomas and
2. tumors characterized by
• excessive ovarian &
• adrenal androgen production

4. Follicular/E phase Ovulation Luteal/E-P phase
1-13 days 14 day 15-28 days
Proliferative Secretory
Main hormone E LH+FSH
surge
E+P

5. Follicular phase Luteal phase
Pregnenolone Pregnenolone
17 OH-pregnenolone Progestrone
Dihydro epiandrosterone 17 OH- Progestrone
Androstenedione  Testosterone
16  OH- estrone Estrone  17 estradiol(major)
Estriol Metabolites Excreted in bile
Synthesis & metabolism of female sex hormones

6. Hypothalamus
-Clomiphene GnRF - Danazol
-feedback - Anterior pituitary
Inhibin - FSH LH
Ovary
Graafian follicle Corpus luteum
Estrogen Progesterone
Tamoxifen - Target Organs - Mifepristone
Control of secretion of female sex hormones
& effect of drugs

7. ESTROGENS
Natural: Phytoestrogens, estradiol, estrone, estriol
Synthetic: To oral effectiveness
• Steroidal-Ethinyl estradiol, Mestranol,
Quinestrol
• Non-steroidal- Diethyl stilbestrol

8. Pharmacokinetics
Mainly oral route  excreted in bile &
reabsorbed from intestineEntero-hepatic
circulation high ratio of hepatic to
peripheral effects
Hepatic effects undesirable actions like ed
synthesis of clotting factors & plasma renin
substrate
Avoided by using alternate routes of adm. like
vaginal creams, transdermal patches

9. Physiological effects of E
• Female maturation: Normal development of
female genital tract, breast & secondary
female sex characters
• Endometrial effects:
• maitenance of mensturation cycle
• necessary for maintenance of pregnancy &
accompanying breast hyperplasia

10. • Skeletal: Pubertal skeletal growth, promotes
epiphyseal closure, anti-resorptive effects
• Metabolic & CV effects:
circulating levels of thyroxine, Fe, Cu
Changes in plasma lipids- HDL, Tgs,
LDL, cholestrol levels
• Enhance coagulability of blood
• Behavioral:  libido, mood

11. Therapeutic uses
• Contraception
• Primary hypogonadism
• Post-menopausal hormonal replacement
therapy
• Other uses

12. • Primary hypogonadism: Primary failure of
development of ovaries, premature
menopause/ menopause, castration, –
estrogen deficient patient
Rx- 0.3mg conjugated estrogen 1-21 days
each month starting from 11-13 yrs (In
primary failure of ovaries)

13. • Post menopausal hormonal replacement
therapy (HRT)
Most beneficial in women who are at risk of
osteoporosis & with vasomotor symptoms
In osteoporosis, E. replacement is preventive
& does not restore bone loss
+ Calcium & Vitamin D & weight bearing
exercises
Beneficial effect seen after continuous use

14. • Vasomotor symptoms: Rx with E. is specific
& very effective
If E. C/I, Medroxy progestrone acetate
s(MPA)
• Prevention of CV disease in
postmenopausal women mediated by
systemic changes in lipoprotein metabolism
& direct effects on BV’s.
• Not proven in many studies as it
es incidence of thromboembolic & Gall
bladder ds.

15. • Urogenital atrophy: E. orally/ locally
vaginal creams & ring devices
Regimens
E+P to women with uterus
E alone to women without uterus/hystrectomy
because risk of endometrial ca. is not there

16. Cyclic regimens : usually preferred
* E for first 25 days
*MPA for last 10-13 days
*Hormone free 5-6 days for withdrawal
bleeding
*hormones can be given continuously
- better compliance

17. • Other uses of E:
• Intractable dysmenorrhea
• Supression of ovarian function in hirsutism
• Amenorrhea d/t excessive secretion of
androgens by ovary

18. Adverse effects
• Major – uterine bleeding
• Nausea & breast tenderness
• Hyperpigmentation
• Migraine
• Gall bladder disease
• Hypertension
• Cancers may occur

19. Tibolone
• It is 19 nor steroid with E+P properties with
weak androgenic activity
• Suppresses menopausal S/S effectively
• No endometrial stimulation noted
• Progestin addition not req.
• Other features of menopause are also
relieved

20. Contraindications of E
• E dependent neoplasms –endometrial/breast
• Undiagnosed genital bleeding
• Liver disease
• Thromboembolic disorders
• Heavy smokers

21. Anti estrogens /
Estrogen lowering therapy

22. • Antiestrogens
Clomiphene
Megestrol
Danazol
• SERMs
• GnRH inhibitors
• Aromatase inhibitors

23. Antiestrogen
Clomiphene – binds to ER and 
Pure E antagonist
MOA: E feedback inhib. Of pituitary blocked
– induces Gn secretion – LH/FSH released
at each pulse ed – ovaries enlarge –
ovulation occurs
Use main in sterility. 50mg daily5days
starting from 5th day of LMP
Other uses: To aid invitro fertilization
Oligospermia- low success rate

24. Adverse effects:
• Polycystic ovaries, multiple pregnancies,
hot flushes, gastric upset, vertigo, Ovarian
tumor risk mb 
Danazol
Suppresses ovarian steroidogenesis and
androgenic effect
es HDL, acne, hirsutism
Therap. uses: Rx of endometriosis,
Fibrocystic breast diseases

25. Megestrol
Used as E lowering therapy in Ca breast
Selective Estrogen Receptor Modulators
(SERMS)
Tamoxifen approved for metastatic breast ca
Raloxifene approved for prevention & Rx of
osteoporosis in PM HRT
Ormiloxifene approved for Dysfunctional
Uterine Bleeding

26. Tamoxifen citrate
MOA: potent E antagonist & weak E actions
Therap. use: as first line hormonal Rx of
breast ca in pre- & post- menopausal
women
Other benefits: Improved bone mass d/t
antiresorptive effect & in lipid profile
Orally effective. 10-20 mg BD
Adverse effects: Risk of endometrial ca  2-3
fold, menstrual irregularities, hot flushes
Less toxic than other anti ca agents

27. Raloxifene
E partial agonist in bone & CV system
Antagonist in endometrium & breast
Approved for osteoporosis in menopause
No  in risk of endometrial ca
Adverse effects are mild. No use in men

28. GnRH agonists
Gonadorelin
Leuprolide
Goserelin
Nafarelin
Histrelin
Given parentral/ intranasally
Given in short courses to prevent risk of
osteoporosis

29. Therapeutic uses:
• Rx of E & androgen dependent ds. Like
metastatic breast & prostate ca
• To suppress premature hypothalamic
activity in precocious puberty
• In steroid responsive gynaecological
disorders like endometriosis, uterine
fibroids, PCOS

30. Aromatase inhibitors
Non steroidal
• Anastrozole
• Letrozole
• Vorozole
Steroidal
• Formestane
• Exemestane
3rd generation
• Aminoglutethemide –more potent & selective

31. Reduce endogenous E by 85% in post
menopausal women
Therap.use: metastatic breast ca
Adverse effects - Generally well tolerated
Hot flushes, genitourinary atrophy