Estrogen, progesterone and testosterone are principal gonadal hormones. Estrogen and progesterone are produced by ovaries whereas testosterone is mainly formed by testes. ESTROGENS Natural estrogens include estradiol(principal and most potent estrogen),estrone and estriol(weakest). Natural estrogens are ineffective orally due to extensive first pass metabolism. Estrogens undergo enterohepatic circulation that is also responsible for hepatic adverse effects(hepatic adenoma and thromboembolism).

1. GONODAL HARMONES
Dr.Raghavendra S.Hegde, Pharm.D(PB)
Lecturer, HSK College of Pharmacy
Bagalkot

2. GONADAL HARMONES
 Estrogen, progesterone and testosterone are principal gonadal hormones.
 Estrogen and progesterone are produced by ovaries whereas testosterone
is mainly formed by testes.
 ESTROGENS
 Natural estrogens include estradiol(principal and most potent
estrogen),estrone and estriol(weakest).
 Natural estrogens are ineffective orally due to extensive first pass
metabolism.
 Estrogens undergo enterohepatic circulation that is also responsible for
hepatic adverse effects(hepatic adenoma and thromboembolism).
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3. Different types of Natural Estrogen
Estrogen Estrone Estradiol Estriol
Known as E1 E2 E3
Potency Intermediate Maximum Minimum
Main
estrogen in
Menopause Reproductive
age group
Pregnancy
Major site of
production
Fat cells Ovaries Liver
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4. Natural Estrogens
• E1 E2 E3
• E1- Estrone – post Menopausal Female
• E2- Estradiol - Reproductive
• E3- Estriol - Pregnancy
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5. EFFECTS OF FEMALE SEX HARMONES
Parameter Estrogen Progesterone
Menstrual Cycle Proliferatory Endometrium Secretory Endometrium
Lipid Profile ↓LDL, ↑HDL, ↑TG ↑ LDL, ↓ HDL
Glucose Tolerance Impair ↑ Insulin Response
Fluid balance Retain Na+ and water ↓Sodium reabsorption
Thromboembolism ↑ Risk by
↑ Factor VII, VIII, IX, X
↓Antithrombin
_
Risk of Breast Cancer Increase Increase
Risk of Endometrial Cancer Increase Decrease
Bone ↓ Resorption -
Bile Lithogenicity Increase -
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Dr.Hegde Lectures(DHL)

6. Indications
• Deficiency of this hormone as seen in postmenopausal
females may result in:
 Osteoporosis
 Hot flushes
 Urogenital atrophy and increased risk of cardiovascular
diseases.
 Major use of estrogens for hormone replacement therapy
(HRT)in post menopausal females.
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7. Indications
• Progesterone is added to HRT to decrease the risk of endometrial
carcinoma. Estrogens can reverse all the features of its deficiency.
• Another important use of estrogens is as a component of oral
contraceptives.
• These can be used in the treatment of dysfunctional uterine
bleeding(DUB),if it is due to estrogen withdrawal.
• Estrogens reduce testosterone production due to feed back inhibition of
LH secretion. This property has been utilized for the treatment of
testosterone dependent tumors like prostatic carcinoma.
• But now a days, GnRH agonists and antagonists are preferred for this
indication.
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8. Adverse effects and interactions
 Increased Risk of endometrial cancer and Breast cancer in females.
 Diabetes, Fluid retention, hepatic adenoma,cholelithiasis, and
predisposition to thromboembolism is seen in both sexes.
 Increased incidence of Cervical and Vaginal adenocarcinoma was noted in
female offspring's(DES) during first trimester of pregnancy.
 Hypospadias in new born babies was noted
 Antimicrobials like ampicilin and enzyme inducers like rifampicin decrease
the effect of estrogen.
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9. SERMS(Selective estrogen receptor modulator)
• These are the agents that act as estrogen agonist in some tissues and
antagonist in other tissues.
• Agonist action is beneficial like decreased resorption and better lipid
profile.
• Deleterious effects like Endometrium and Breast increased risk of
cancer predisposition to VTE.
• Eg. Include: Clomiphene, Tamoxifen, Doloxifen,
raloxifene,Bazedoxifene
9
Mnemonic
Tamoxifen has
Beneficial Effect on three B
Bone(↓Resorption)
Breast(↓ Carcinoma)
Blood (↑ HDL & ↓LDL)

10. • Raloxifene and Bazedoxifene are used for osteoporosis.
• Raloxifene also possess beneficial effects on lipid profile, breast and
endometrium.
• Major adverse effects include increased predisposition to
thromboembolism.
• Ospemifene is a new SERM indicated for dyspareunia due to menopause
• Prasterone is an inactive steroid that is converted to estrogens and
androgens in the body. It is indicated for the treatment of dyspareunia due
to vulvovaginal atrophy.
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13. PROGESTERONE
AKA Potency Androgenic
Activity
1st Generation Estranes(Norethindron
e, Norethinodrel,
Lynestrenol)
+ + + +
2nd Generation Gonanes(Norgestrel) + + + +
3rd Generation Desogestrel,Norgestim
ategestodene
+ + + +
4th Generation Nomegestrel,
Drospirenone
+ + + + Anti- Androgenic
Progesterone is the most important progestin in humans. It is primarily secreted by
corpus luteum. It is classified as
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14. 1st Generation 2nd Generation
Nor-Ethindrone
Nor-Ethinodrel
Norgesterolerol
Levonorgest [ LNG]
3rd Generation 4th Generation
Desogestrel
Norgestimate
Nomegestrel
Drospirenone Antimineral
Corticoid activity
As the generation increases the Potency Increases
Most of the progesterone's contain Androgenic activity
It decreases as per generation.
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15. USES of Progestins
• Major indications of progesterone are for oral Contraceptives
and HRT for which these are combined with estrogens.
• Progestins are added to decrease the risk of endometrial and
ovarian carcinoma.
• They are also used for secondary amenorrhea, abnormal
uterine bleeding, premature labor, and luteal support to treat
infertility.
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16. SELECTIVE PROGESTERONE RECEPTOR MODULATOR(SPRM)
• Mifepristone,onapristone,ulipristal and asoprisnil are the drugs affecting
progesterone receptors.
• Mifepristone is a SPRM with mainly antagonistic activity and some
agonistic activity on progesterone receptors.
• It also has glucocorticoid and androgen receptor blocking activity.
• It has a long t 1/2of 20 hours.
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17. Its uses are: -
• Medical termination of pregnancy:
• Oral dose of 600 mg mifepristone with oral
misoprostol(400ug) effectively terminates pregnancy upto 49
days in 95%of patients.
• Most severe adverse effect is vaginal bleeding.
• Recently, low dose mifepristone(200 mg)with oral
misoprostol(800 ug)is indicated for termination of pregnancy
upto 63 days.
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18. Its uses are: -
• Single 600 mg dose is an effective emergency contraceptive. -
It is recommended for treatment of Cushing's syndrome for
patients with ectopic ACTH secretion or adrenal inoperable
carcinoma who failed to respond to other treatments.
• Other potential uses include endometriosis, breast Cancer,
meningioma(containing glucocorticoid or progesterone
receptors),and fibroids.
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19. MIFEPRISTONE
• SPRM(Selective Progesterone Receptor Modulator)
• Progesterone R +/- Endometrium
• Glucocortoid R Antagonist
• Androgen -
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22. Hormonal Contraceptives
• Combined oral contraceptives
These contain both estrogen and progesterone.
• Most commonly used estrogen in combined OCP's is ethinyl estradiol.
• On the basis of amount of estrogen, combined oral contraceptives can be
classified as
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Type of OCP Amount of Ethinyl
estradiol
Standard dose 50 mcg
Low dose 30-35 mcg
Very low dose 20 mcg

23. Combined oral contraceptives
• Most commonly used progesterone in combined OCP his
levonorgestrel LNG.
• Combined OCP maybe:
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Monophonic: Content of oestrogen and progesterone remain same in all pills ( for
21 days)
Biphasic: Content of progesterone is different in pills for first 10 days and that for
11 to 21 days.
Triphasic: Content of progesterone is gradually increased. It is lowest in first phase
(7 to 11 days) and further increase in 3rd phase(12-21days)

24. • Biphasic and triphasic pills progesterone content without compromising
efficacy.
This pills decrease the risk of breakthrough bleeding.
• Main mechanism of combined OCP is to cause feedback inhibition of
pituitary( causing abolition of LH surge) resulting in inhibition of ovulation.
• Other mechanism include thickening of cervical mucus, decreased motility
and secretions of the fallopian tubes and making endometrium
unfavourable for implantation.
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Combined oral contraceptives

25. (1) Inhibition of
Ovulation
COP(E+P)
1
2
Inhibition of
Ovum
3
Drug make cervical fluid thick
and hostile POP (MINI pills)
4
Remove the
implantation/disloding of
implantation. eg.Emergency
pills, post coital pills,
morning after pills
4
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26. Drugs MAIN MECHANISM
COMBINED OCP[ E+P] Inhibition of Ovulation
PROGESTERONE ONLY
PILLS/MINIPILLS
Cervical Mucus Thickening and
Hostile
EMERGENCY/POST
COITAL/MORNING AFTER PILLS
Dislodging of implantation
I.COMBINED ORAL CONTRACEPTIVE PILLS
ESTROGEN : ETHINYL ESTRADIOL
PROGESTERONE : LEVONORGESTEROL
Major Mechanism of different OCP’s
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27. DOSAGE:
 1 Tab daily for 21 days from 1st day of menstrual cycle
 No tablet for next 7 days
 To ↑ compliance
• 28 Tablets strip with
• 1st 21 tablets containing drug
• Next 7 days containing Fe
1.If 1 Tablet is missed Take 2 tablets on next day
2.If 2 Tablet is missed Discard remaining tablets & start a fresh and
practice other method of contraception with it.
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28. Combined oral contraceptives
• Combined OCP started on first day of menstrual cycle and given for 21
days.
• To allow withdrawal bleeding given( without hormones) for next 7 days.
• Ovulation returns within 3 months of stopping OCP used in 90% of cases.
• OCP’s are contraceptives of choice for
• Newly married couples
• After evacuation of molar pregnancy
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29. BREAKTHROUGH BLEEDING
 Bleeding at 1-21 days.
 Prevented by PHASIC PILLS.
 Gradual increase of progesterone from 1-21 days
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30. Progesterone only pills (mini pills)
• These contain low dose of progestin without any estrogen
• these are less effective than combined oral contraceptives.
•
• Mini pills are preferred in women where estrogen is contraindicated
Smokers
> 35 years of Age
Risk Factors of Thromboembolism
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31. Progesterone only pills (mini pills)
 Mini pills are oral contraceptives of choice for
Lactating women
sickle cell anemia
Seizure disorder
Progesterone only pills are given daily without any break.
 Thickening of cervical mucus is major mechanism of mini pills.
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32. II. POP/MINIPILLS :
• CONTAINS LNG
• INDICATIONS: 1: Thromboembolism risk
2:Lactation: (contraceptive of Choice)
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33. III.Emergency contraceptives
1. COC : 2 tablets at start + 2 tablets after 12 hrs.
1. POP(LNG): 1 tablet at start + 1 tablet after 12 hrs
or
: 2 tablet at start
3.Mifepristone (SPRM)Selective Progesterone Receptor Modulator
Uses: 1: Emergency Contraception
2: Induction of abortion.
Above 3 drugs should be used within 72 hrs of unprotected sex.
4.ULIPRASTAL
LNG and Uliprastal Can be used within 120 hrs, however LNG has very low
efficacy
5. IUD
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34. III.Emergency contraceptives(Post-coital pills ;
Morning after pills)
Method Use within Dose and Duration
1.Levonorgesterol(LNG
)
72 hours* 1.5 mg(oral) single
dose
2.OC pills 72 hours 2tablets followed by
another 2within 12
hours
3.Mifepristone 72 hours 600 mg oral single
dose
4.Ulipristal 120 hours 30 mg oral single dose
5.IUD 5 days -------
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35. MILD MODERATE SEVERE
N: Nausea ACNE CVS(THROMBOEMBOLI
SM)
O:Odema WEIGHT GAIN CNS(DEPRESSION)
R: Recurrent Headache CHLOASMA CHOLESTASIS
M: Mastalgia CANCERS
A: Abnormal Bleeding ↑BREAST CANCER
L: Loss of withdrawl
Bleeding
↑CERVICAL
CARCINOMA
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Adverse effects

36. CONTRA INDICTIONS
 Undiagnosed Vaginal Bleeding
 H/O Breast Cancer
 H/O Endometrial Cancer
 Liver Dysfunction
 Thrombo embolic disorders
 Endometriosis
 Fibroids
 Porphyrias
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41. HPG Axis
• Hypothalamus
• Pituitary
• Ovary
• Estrogen Receptor antagonist at pituitary
• Indication Anovulatory infertility
GnRH
Progesterone/
Estrogen
FSH/LH
- - Feedback
Inhibition
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