1. The document discusses female sex hormones including estrogens, progestins, and their synthesis and metabolism in the body. 2. It covers the functions of the ovaries and disturbances that can occur due to stress or eating/exercise disorders. 3. Organic causes of disturbances like pituitary tumors and ovarian/adrenal tumors that produce excessive hormones are also mentioned. 4. The use of estrogens, progestins, antiestrogens, selective estrogen receptor modulators, gonadotropin-releasing hormone agonists, and aromatase inhibitors in conditions like contraception, menopausal symptoms, breast and prostate cancer, and other gynecological disorders is summarized.

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