- Androgens like testosterone and synthetic analogs cause male secondary sex characteristics. Testosterone is produced in testes and adrenals and binds to androgen receptors. - Testosterone has androgenic effects like development of male reproductive tract and secondary sex characteristics. It also has anabolic effects like muscle building. - Androgens are used to treat conditions like hypogonadism and wasting diseases. Synthetic anabolic steroids have higher anabolic effects. Anti-androgens like danazol and cyproterone acetate are used to treat conditions like endometriosis by inhibiting androgen action.

1. Androgens, Oestrogens, ProgestinsAndrogens, Oestrogens, Progestins
and Hormonal Contraceptivesand Hormonal Contraceptives
Dr. D. K. BrahmaDr. D. K. Brahma
Associate ProfessorAssociate Professor
Department of PharmacologyDepartment of Pharmacology
NEIGRIHMS, ShillongNEIGRIHMS, Shillong

2. IntroductionIntroduction
 Substances which cause secondary sex characteristicsSubstances which cause secondary sex characteristics
in Malein Male
 Natural Androgens:Natural Androgens:

From Testes:From Testes:
• Testosterone (5-12 mg daily)Testosterone (5-12 mg daily)
• Dihydrotestosterone (more active) by 5Dihydrotestosterone (more active) by 5 αα-reductase-reductase

From Adrenal cortex: (weak androgens)From Adrenal cortex: (weak androgens)
• DehydroepiandrosteroneDehydroepiandrosterone
• AndrostenedioneAndrostenedione
{Females – 0.25 – 0.5 mg/day (ovary + adrenals)}{Females – 0.25 – 0.5 mg/day (ovary + adrenals)}

Androsterone – metabolite of testosteroneAndrosterone – metabolite of testosterone
 Synthetic androgens:Synthetic androgens:

Methyltestosterone, FluoxymesteroneMethyltestosterone, Fluoxymesterone

Propionate and enanthatePropionate and enanthate

3. TestosteroneTestosterone
 Produced from cholesterol primarily by Leydig cells in testesProduced from cholesterol primarily by Leydig cells in testes
 Secreted at adult levels during 1st trimesterSecreted at adult levels during 1st trimester11, during neonatal life, during neonatal life22,,
continually after pubertycontinually after puberty33
 Bound in plasma to albumin & sex hormone binding globulinBound in plasma to albumin & sex hormone binding globulin
(SHBG)(SHBG)
 Can be converted to the more potent, 5α-dihydrotestosteroneCan be converted to the more potent, 5α-dihydrotestosterone
(DHT), which is responsible for many of the responses to(DHT), which is responsible for many of the responses to
testosterone in the urogenital tract (e.g. prostate gland hyperplasia)testosterone in the urogenital tract (e.g. prostate gland hyperplasia)
 Binds to and activates a single androgen receptor (AR)Binds to and activates a single androgen receptor (AR)
 Androgen receptors are present in many tissues includingAndrogen receptors are present in many tissues including
reproductive tissue, skeletal muscle, brain, kidney etc.reproductive tissue, skeletal muscle, brain, kidney etc.
1 2 3

4. Testosterone 17-alkyl substitution Methyltestosterone
Fluoxymesterone
• All androgens contain a Testosterone structures
• Testosterone has 19-carbons and in general its a steroidal
structure

5. Cholesterol
Pregnenolone
Progesterone
Corticosterone
11-Desoxy-
corticosterone
18-Hydroxy-
corticosterone
ALDOSTERONE
17-α- Hydroxy
pregnenolone
11- Desoxy-
cortisol
17- Hydroxy
progesterone
21,β hydroxylase
CORTISOL
11,β hydroxylase
Dehydro-epi
androsterone
Andro-
stenedione
Oestrone
Oestriol
TESTOSTERONE OESTRADIOL
ACTH

6. Regulation of SecretionRegulation of Secretion
• LH – Testosterone secretion
• FSH – Spermatogenesis
• High testosterone – inhibits LH
• Estrogen – feedback inhibition
• Inhibin – FSH inhibition
• Plasma level of Testosterone:
0.3 to 1 mcg/dl (male)
20 to 60 ng/dl (female)

7. Biological Effects - TestosteroneBiological Effects - Testosterone
Androgenic Effects:Androgenic Effects:
 In the foetus, testosterone promotes development of maleIn the foetus, testosterone promotes development of male
reproductive tract – internal genitalia, vas deferens, epididymis andreproductive tract – internal genitalia, vas deferens, epididymis and
external genitalia (sex differentiation)external genitalia (sex differentiation)
 During puberty, testosterone promotes development of :During puberty, testosterone promotes development of :

primary sexual characteristics (e.g. enlargement of penis, scrotum andprimary sexual characteristics (e.g. enlargement of penis, scrotum and
testes)testes)

secondary sexual characteristics (e.g. male body shape, facial/pubicsecondary sexual characteristics (e.g. male body shape, facial/pubic
hair, deeper pitch of voice)hair, deeper pitch of voice)
 Adulthood: Baldness, BHP, Prostatic cancerAdulthood: Baldness, BHP, Prostatic cancer
Testes:Testes: Promotion of spermatogenesis and maturation of spermPromotion of spermatogenesis and maturation of sperm
 Moderately high dose causes testicular atrophy by inhibiting GnModerately high dose causes testicular atrophy by inhibiting Gn
secretionsecretion

8. Testosterone – anabolic effectsTestosterone – anabolic effects
 Pubertal spurt of growth at puberty – both boy and girlPubertal spurt of growth at puberty – both boy and girl
 Bone growth – thickness and lengthBone growth – thickness and length
 Oestrogen from testosterone – fuse of bones andOestrogen from testosterone – fuse of bones and
mineralizationmineralization
 Muscle building – if aided by exerciseMuscle building – if aided by exercise
 Positive nitrogen, minerals and water balance – increasePositive nitrogen, minerals and water balance – increase
in weightin weight
 Increase in appetiteIncrease in appetite
 Acceleration of erythropoiesisAcceleration of erythropoiesis

9. Androgens – Targets of ActionAndrogens – Targets of Action

10. Mechanism of ActionMechanism of Action
Androgen receptor:Androgen receptor:
 Both, testosterone and DH testosterone – act via AndrogenBoth, testosterone and DH testosterone – act via Androgen
receptors (AR) – nuclear receptor super familyreceptors (AR) – nuclear receptor super family
 55 αα-reductase 1 and 2-reductase 1 and 2
 Ligand binding and DNA binding domainsLigand binding and DNA binding domains
 Mutations in AR: Incomplete sexual developmentMutations in AR: Incomplete sexual development

Kennedy`s disease: in spinal andKennedy`s disease: in spinal and
bulbar muscle atrophybulbar muscle atrophy
Estrogen Receptor:
• Teststerone converts to
estrogen by CYP19
• Deficiency of CYP19 and
estrogen receptor – failure to
fuse long bones,
osteoporosis etc.

11. T DHT DHT- R
T- R
R
R
T- R
Nucleus
90%
10%
5- α
reductase
cytoplasm

12. Androgen - PharmacokineticsAndrogen - Pharmacokinetics
 Absorption:Absorption: undergoes high firstundergoes high first
pass metabolism. Therefore IMpass metabolism. Therefore IM
injections or synthetic preparationsinjections or synthetic preparations
are usedare used
 Transport:Transport: highly protein boundhighly protein bound
(98%, SHBG, albumin)(98%, SHBG, albumin)
 Metabolism:Metabolism:

by liver enzymes : androsteroneby liver enzymes : androsterone
& etiocholanolone& etiocholanolone

excretion by urine afterexcretion by urine after
conjugationconjugation

small quantity of oestrogen alsosmall quantity of oestrogen also
produced from testosteroneproduced from testosterone
Methyltestosterone, FluoxymesteroneMethyltestosterone, Fluoxymesterone
metabolized slowlymetabolized slowly

13. Therapeutic Androgen PreparationsTherapeutic Androgen Preparations
 Testosterone is ineffective orally (inactivated by liver), and is usuallyTestosterone is ineffective orally (inactivated by liver), and is usually
given as i.m. injections of testosterone estersgiven as i.m. injections of testosterone esters

Esterification of fatty acid at 17-hydroxyl groupEsterification of fatty acid at 17-hydroxyl group

Examples- propionate (25-50 mg), enanthate (100 mg depotExamples- propionate (25-50 mg), enanthate (100 mg depot
preparations)preparations)

Undecanoate in oil - orallyUndecanoate in oil - orally

effects last for 2-3 weekseffects last for 2-3 weeks
 Transdermal preparations: Implants, capsules and patches mayTransdermal preparations: Implants, capsules and patches may
improve complianceimprove compliance

more stable levels and symptoms, effects last for monthsmore stable levels and symptoms, effects last for months

14. Therapeutic Uses of AndrogensTherapeutic Uses of Androgens
 Androgen replacement therapy (ART)Androgen replacement therapy (ART)
 ART uses derivatives of testosterone, rather than syntheticART uses derivatives of testosterone, rather than synthetic
Androgens, because they are safe, effective and easy to monitorAndrogens, because they are safe, effective and easy to monitor
1.1. Androgen deficiency:Androgen deficiency: clinical diagnosis confirmed by hormone assaysclinical diagnosis confirmed by hormone assays

is usually caused byis usually caused by
• underlying testicular disorders (high LH, but low testosterone levels)underlying testicular disorders (high LH, but low testosterone levels)
• hypothalamic-pituitary disorders (low LH and low testosteronehypothalamic-pituitary disorders (low LH and low testosterone
levels)levels)
 Goal: Mimic the normal testosterone concentration as closely as possibleGoal: Mimic the normal testosterone concentration as closely as possible
(serum concentration monitoring)(serum concentration monitoring)
 If untreated, does not shorten life expectancy, but is associated withIf untreated, does not shorten life expectancy, but is associated with
significant morbidity (ambiguous genitalia, delayed puberty & infertility)significant morbidity (ambiguous genitalia, delayed puberty & infertility)
 Treated by androgen replacement therapy (ART), usually for the remainderTreated by androgen replacement therapy (ART), usually for the remainder
of life. The aim is to restore tissue androgen exposure by using the naturalof life. The aim is to restore tissue androgen exposure by using the natural
androgen testosteroneandrogen testosterone

15. Uses – contd.Uses – contd.
2.2. HypopituitarismHypopituitarism

Monitoring at anticipated time of pubertyMonitoring at anticipated time of puberty
2.2. AIDS related muscle wastingAIDS related muscle wasting
3.3. Hereditary angioneurotic edema (methyltestosterone)Hereditary angioneurotic edema (methyltestosterone)
4.4. AgeingAgeing
Misuse:Misuse: involves prescription with no acceptable medicalinvolves prescription with no acceptable medical
indicationindication
 Examples of misuse include:Examples of misuse include:

male infertilitymale infertility

male sexual dysfunction or impotencemale sexual dysfunction or impotence

““male menopause” (andropause)male menopause” (andropause)
 no convincing evidence that androgen therapy is eitherno convincing evidence that androgen therapy is either
effective treatment or safe for older men unless thereeffective treatment or safe for older men unless there
is frank androgen deficiencyis frank androgen deficiency

16. Androgens – Adverse EffectsAndrogens – Adverse Effects
 Virilization:Virilization:

may occur in women receiving relatively high dosesmay occur in women receiving relatively high doses
for prolonged periods, such as for estrogen-for prolonged periods, such as for estrogen-
dependent mammary carcinomadependent mammary carcinoma
 Cholestatic JaundiceCholestatic Jaundice

may be produced by steroids possessing a 17-alphamay be produced by steroids possessing a 17-alpha
methyl group – oral Vs parenteralmethyl group – oral Vs parenteral
 Priapism (sustained erection)Priapism (sustained erection)
 OligospermiaOligospermia
 Edema--via promotion of salt and water retention.Edema--via promotion of salt and water retention.
 Precocious puberty and short staturePrecocious puberty and short stature
 AcneAcne
 Hepatic carcinoma - oralHepatic carcinoma - oral
 Gynaecomastia – children and liver diseaseGynaecomastia – children and liver disease

17. Androgens - contraindicationsAndrogens - contraindications
 Carcinoma of Prostate and male BreastCarcinoma of Prostate and male Breast
 Liver and Kidney diseasesLiver and Kidney diseases
 PregnancyPregnancy
 CHF, epilepsy and migraineCHF, epilepsy and migraine

18. Anabolic SteroidsAnabolic Steroids
 Synthetic analogues – higher anabolic butSynthetic analogues – higher anabolic but
lower androgenic activity (1: 3 ratio)lower androgenic activity (1: 3 ratio)
 Examples;Examples;

Nandrolone propionate 10-25 mg/ml (10 – 50Nandrolone propionate 10-25 mg/ml (10 – 50
mg IM/week) – inj. Durabolinmg IM/week) – inj. Durabolin

Nandrolone decanoate 25-100 mg/ml (25-Nandrolone decanoate 25-100 mg/ml (25-
100mg/week) – inj. Decadurabolin100mg/week) – inj. Decadurabolin

Stanazolol (2mg tablets (2-6 mg/day)Stanazolol (2mg tablets (2-6 mg/day)

19. Anabolic Steroids – TherapeuticAnabolic Steroids – Therapeutic
usesuses
1.1. Catabolic states: Acute illness, severeCatabolic states: Acute illness, severe
trauma, major surgerytrauma, major surgery
2.2. Renal insufficiency – frequency ofRenal insufficiency – frequency of
dialysisdialysis
3.3. Osteoporosis – elderly malesOsteoporosis – elderly males
4.4. Suboptimal growth in boysSuboptimal growth in boys
5.5. AnaemiaAnaemia
6.6. Perfomance enhancementPerfomance enhancement

20. Anti-androgensAnti-androgens
 DanazolDanazol
 Cyproterone acetateCyproterone acetate
 FlutamideFlutamide
 Finasteride attenuatedFinasteride attenuated

21. DanazolDanazol
 Ethisterone derivative effective orallyEthisterone derivative effective orally
 FSH & LH release in both sexes decrease –FSH & LH release in both sexes decrease –
inhibition of testicular/ovarian functioninhibition of testicular/ovarian function
 Binding of steroids to receptors decreaseBinding of steroids to receptors decrease
 Weak androgenic, anabolic, progestational & glucocorticoid actionWeak androgenic, anabolic, progestational & glucocorticoid action
Uses:Uses:

EndometriosisEndometriosis

MenorrhagiaMenorrhagia

Fibrocystic breast diseaseFibrocystic breast disease

Hereditary angioneurotic oedemaHereditary angioneurotic oedema

GynecomastiaGynecomastia

Infertility: attenuatedInfertility: attenuated
Preparations:Preparations:

50. 100 and 200 mg. tablets50. 100 and 200 mg. tablets

Dose is 200 – 600 mg/dayDose is 200 – 600 mg/day
Side effects: Dose related
• Amenorrhea (High doses)
• Androgenic effects - Decreased breast
size, hirsutism, weight gain etc.
• Hot flashes, night sweating, cramps

22. Cyproterone acetateCyproterone acetate
 Progesterone like activity – inhibits LH causingProgesterone like activity – inhibits LH causing
antiandrogenic actionantiandrogenic action
 Competes with dihydroteststerone for intracellularCompetes with dihydroteststerone for intracellular
receptorreceptor
Uses:Uses:
 AcneAcne
 Male pattern of baldnessMale pattern of baldness
 hirusitismhirusitism
 Ca. of prostateCa. of prostate
 Virilizing syndromeVirilizing syndrome
 Precocious pubertyPrecocious puberty
 Inappropriate behaviourInappropriate behaviour

23. FlutamideFlutamide
 Non-steroidal anti-inflammatory and noNon-steroidal anti-inflammatory and no
hormonal activity but specific antiandrogenichormonal activity but specific antiandrogenic
actionaction
 Antagonise androgens by competitive block – 2-Antagonise androgens by competitive block – 2-
hydroxyflutamidehydroxyflutamide

Accessory sex organsAccessory sex organs

PituitaryPituitary
Uses:Uses:
 Cancer of prostate along with GnRH agonistCancer of prostate along with GnRH agonist
 Female hirusitismFemale hirusitism
Dose: 250 mg tds.Dose: 250 mg tds.

24. FinasterideFinasteride
 MOA:MOA: Competitive inhibitor of 5Competitive inhibitor of 5 αα-reductase-reductase

Selective ofSelective of 55 αα-reductase type-2 isoenzyme-reductase type-2 isoenzyme

Mainly acts on urogenital tract (prostate) – DHT level loweredMainly acts on urogenital tract (prostate) – DHT level lowered
but not plasma Testosterone levelbut not plasma Testosterone level
 Uses:Uses:
1.1. Benign prostatic hypertrophy – decrease in prostate volume,Benign prostatic hypertrophy – decrease in prostate volume,
improved urinary flow, reversion of disease progressionimproved urinary flow, reversion of disease progression
– Withdrawal results in regrowth – prolonged therapyWithdrawal results in regrowth – prolonged therapy
1.1. Male pattern baldnessMale pattern baldness
– Kinetics:Kinetics: effective orally, metabolized in liver (t1/2 – 4-6effective orally, metabolized in liver (t1/2 – 4-6
hrs)hrs)
– Side effects:Side effects: loss of libido, impotence, decreasedloss of libido, impotence, decreased
ejaculationejaculation
– Doses:Doses: 5 mg OD (BHP) or 1 mg OD in baldness5 mg OD (BHP) or 1 mg OD in baldness

25. Erectile Dysfunction DrugsErectile Dysfunction Drugs
PDE-5 Inhibitors:PDE-5 Inhibitors: Sidenafil, tadalafilSidenafil, tadalafil

Nitric oxide (NO) pathwayNitric oxide (NO) pathway

26. SidenafilSidenafil
 Absorbed orally and half-life is 4 HrsAbsorbed orally and half-life is 4 Hrs
 Inhibits PDE5 in the corpus cavernosa of the penisInhibits PDE5 in the corpus cavernosa of the penis
 50mg 1 h before sexual activity50mg 1 h before sexual activity
 Potentiate nitrate’s hypotension activityPotentiate nitrate’s hypotension activity
 Ketoconazole, erythromycin, Verapamil increases itsKetoconazole, erythromycin, Verapamil increases its
level – due to CYP3A4 inhibitionlevel – due to CYP3A4 inhibition
 Renal & hepatic disease increases its levelRenal & hepatic disease increases its level
 Side effects:Side effects:
headache, flushing, dyspepsia, myalgia, loose motionheadache, flushing, dyspepsia, myalgia, loose motion
 Other Uses:Other Uses: Pulmonary hypertensionPulmonary hypertension

27. Oestrogens

28. OestrogensOestrogens

29. IntroductionIntroduction
 Oestrogens include the natural hormonesOestrogens include the natural hormones
as well as semi-synthetic and syntheticas well as semi-synthetic and synthetic
(stilbene) agents(stilbene) agents
 Oestrogens are used as hormone:Oestrogens are used as hormone:

replacement therapy (menopause)replacement therapy (menopause)

in oncologyin oncology

contraceptivescontraceptives
 Most estrogen in the female is produced inMost estrogen in the female is produced in
the ovaries by thethe ovaries by the theca internatheca interna and theand the
granulosagranulosa cells of the folliclescells of the follicles

30. CH3
OH
H
H
H
HO
ESTRADIOL
CH3
H
H
H
HO
O
ESTRONE
CH3
OH
H
H
H
HO
OH
ESTRIOL
Oxidized in liver
hydroxylation
Natural Oestrogens
1.
2.
3.

31. Synthetic oestrogensSynthetic oestrogens
 Steroidal:Steroidal:

Ethinyl estradiolEthinyl estradiol, Mestranol and Tibolone, Mestranol and Tibolone
 Nonsteroidal:Nonsteroidal:

Diethinylstilbestrol, Hexestrol and DienestrolDiethinylstilbestrol, Hexestrol and Dienestrol

32. Regulation of SecretionRegulation of Secretion
 Daily secretion: 10 toDaily secretion: 10 to
100 mcg per day100 mcg per day
 During pregnancy –During pregnancy –
large quantity bylarge quantity by
placenta – upto 30placenta – upto 30
mg per daymg per day
 Post menopausal: 2 –Post menopausal: 2 –
10 mcg per day only10 mcg per day only

33. Actions of OestrogensActions of Oestrogens
 On sexual organs (primary and secondary sexual characteristics)On sexual organs (primary and secondary sexual characteristics)
 Brings about pubertal changes in vagina, fallopian tube and uterus –Brings about pubertal changes in vagina, fallopian tube and uterus –
growthgrowth

Vagina: cornification of epithelial cells with thickening and stratificationVagina: cornification of epithelial cells with thickening and stratification
of epitheliumof epithelium

Ovaries : stimulate follicular growth; small doses cause an increase inOvaries : stimulate follicular growth; small doses cause an increase in
weight of ovary; large doses cause atrophyweight of ovary; large doses cause atrophy

Cervix: Rhythmic contractions of uterus and fallopian tube - increase ofCervix: Rhythmic contractions of uterus and fallopian tube - increase of
cervical mucous and alkaline watery secretion with a lowered viscositycervical mucous and alkaline watery secretion with a lowered viscosity
(favoring sperm access)(favoring sperm access)
 Secondary Sex CharactersSecondary Sex Characters
 Metabolic effects: AnabolicMetabolic effects: Anabolic

34. Oestrogens PhysiologyOestrogens Physiology

35. Other Pharmacological ActionsOther Pharmacological Actions
 Bone:Bone: Important for maintaining bone mass – increasedImportant for maintaining bone mass – increased
expression of bone mass proteins (osteocalcin, alkalineexpression of bone mass proteins (osteocalcin, alkaline
phosphatase)phosphatase)

Generation of vit.D3 – induction of renal hydroxylaseGeneration of vit.D3 – induction of renal hydroxylase
enzymeenzyme
 OedemaOedema – salt and water retention– salt and water retention
 Increased LDL and decreased HDL levelIncreased LDL and decreased HDL level
 Increased coagulability: II, VII, IX and XIncreased coagulability: II, VII, IX and X
 Lithogenicity of BileLithogenicity of Bile
 Increased SHBG, TBG and CBGIncreased SHBG, TBG and CBG

36. Mechanism of ActionMechanism of Action
 2 ERs are –2 ERs are – ERERαα and ERßand ERß
 ERERαα - uterus, vagina, breast and blood vessels- uterus, vagina, breast and blood vessels
 ERß – Prostate and OvariesERß – Prostate and Ovaries
 Work via a steroid hormone mechanism.Work via a steroid hormone mechanism.
 Entering the target cells and binding to specific cytosolicEntering the target cells and binding to specific cytosolic
receptorsreceptors
 The steroid-receptor complex is then translocated to theThe steroid-receptor complex is then translocated to the
nucleusnucleus
 Where it alters gene expressionWhere it alters gene expression
 Coactivator proteins and corepressor proteinsCoactivator proteins and corepressor proteins

37. Oestrogen - KineticsOestrogen - Kinetics
 Absorbed orally, but quick metabolism –Absorbed orally, but quick metabolism –
natural ones except ethinyl estradiolnatural ones except ethinyl estradiol
 All are absorbed transdermallyAll are absorbed transdermally
 Bound to plasma protein (SHBG)Bound to plasma protein (SHBG)
 Conjugated with glucoronic acid andConjugated with glucoronic acid and
excreted in urineexcreted in urine
 Enterohepatic circulation – deconjugationEnterohepatic circulation – deconjugation
in intestinein intestine

38. Oestrogen preparationsOestrogen preparations
 Preferred route is oral, but sometimes parenteralPreferred route is oral, but sometimes parenteral
when large doses are requiredwhen large doses are required
 All estrogen preparations are available – tabletAll estrogen preparations are available – tablet
and injectionsand injections
 Some examples:Some examples:

EE: 0.01, 0.05, 1 mg tab for menopauseEE: 0.01, 0.05, 1 mg tab for menopause

Conjugated estrogens: 0.625,1.25 mg tab for DUB orConjugated estrogens: 0.625,1.25 mg tab for DUB or
injections 25 mg/mlinjections 25 mg/ml

Mestranol: 0.1 mg tabs to convert to EEMestranol: 0.1 mg tabs to convert to EE

Estriol succinate: 1mg/gm creamEstriol succinate: 1mg/gm cream

39. Transdermal PatchesTransdermal Patches
 Sizes: 5, 10 and 20 sq. cm –Sizes: 5, 10 and 20 sq. cm –
0.025, 0.05 and 1 mg/day0.025, 0.05 and 1 mg/day
 Menopausal womenMenopausal women
 Usual dose: 0.5 mg/dayUsual dose: 0.5 mg/day
 Cyclic therapyCyclic therapy
 Estrogen + Progestin patchesEstrogen + Progestin patches

40. Therapeutic UsesTherapeutic Uses
 Hormone Replacement Therapy to Menopause womanHormone Replacement Therapy to Menopause woman
 Problems of menopause:Problems of menopause:

Vasomotor disturbancesVasomotor disturbances

Urogenital atrophyUrogenital atrophy

Osteoporosis and fracturesOsteoporosis and fractures

Dermatological changesDermatological changes

Risk of cardiovascular diseasesRisk of cardiovascular diseases
 Dosage: Oestrogen equivalent to 0.625 mg of EE/day inDosage: Oestrogen equivalent to 0.625 mg of EE/day in
cyclical mannercyclical manner

Progestin preparation (medroxy progesterone/norethisterone) isProgestin preparation (medroxy progesterone/norethisterone) is
used – 2.5 mg dailyused – 2.5 mg daily

TTS preparations may be preferredTTS preparations may be preferred

41. HRT IndicationsHRT Indications
 Benefits: (Indications)Benefits: (Indications)

Vasomotor and other symptoms of perimenopausal period –Vasomotor and other symptoms of perimenopausal period –
smallest effective dosesmallest effective dose

Post hysterectomy patients – estrogen onlyPost hysterectomy patients – estrogen only

Young woman with premature menopauseYoung woman with premature menopause

Prevention of osteoporosis and fracturesPrevention of osteoporosis and fractures
 Facts:Facts:

No protection against CVS diseasesNo protection against CVS diseases

No protection against cognitive decline – may increaseNo protection against cognitive decline – may increase

Increase in risk of breast cancer, gall stone, migraineIncrease in risk of breast cancer, gall stone, migraine
 Tibolone:Tibolone:

Developed specifically for HRTDeveloped specifically for HRT

Estrogenic and progestitional propertyEstrogenic and progestitional property

Dose is 2.5 mg dailyDose is 2.5 mg daily

42. Selective Estrogen Receptor
Modulators (SERMs)

43. Clomiphene Citrate (Antiestrogen)Clomiphene Citrate (Antiestrogen)
 The “Fertility pill” - pure antagonist ofThe “Fertility pill” - pure antagonist of
ESTROGEN receptor in all human tissuesESTROGEN receptor in all human tissues
 MOA: Gn secretion and FSHMOA: Gn secretion and FSH

Used in women withUsed in women with unexplained infertilityunexplained infertility oror
anovulatoryanovulatory infertilityinfertility

Bind to both, ERBind to both, ERαα and ERß receptorsand ERß receptors

Blocks estrogenic feedback inhibition of pituitary andBlocks estrogenic feedback inhibition of pituitary and
induces Gn secretioninduces Gn secretion

Increase in amount of secretion of FSH/LH at eachIncrease in amount of secretion of FSH/LH at each
secretary pulsesecretary pulse

Creates favorable atmosphere (ovarian stimulation)Creates favorable atmosphere (ovarian stimulation)
for ovulation in ovariesfor ovulation in ovaries

44. Clomiphene Citrate – contd.Clomiphene Citrate – contd.
 Dosage:Dosage:

50 mg OD from 550 mg OD from 5thth
day onwards for 5 daysday onwards for 5 days

Continued for 2-3 cyclesContinued for 2-3 cycles

Conception occurs within 4-6 cyclesConception occurs within 4-6 cycles

If no, dose increasedIf no, dose increased
 Other Uses:Other Uses:

Assisted reproduction (to develop multiple eggs)Assisted reproduction (to develop multiple eggs)

Artificial insemination (irregular ovulation)Artificial insemination (irregular ovulation)
(Clomiphene Challenge Test)(Clomiphene Challenge Test)

Oligospermia (25 mg daily for 6 months – 6 daysOligospermia (25 mg daily for 6 months – 6 days
rest))rest))

45. Tamoxifen (SERM)Tamoxifen (SERM)
 Actions:Actions:

Is a competitive antagonist to estrogen at receptors in theIs a competitive antagonist to estrogen at receptors in the
breast.breast.

Partial agonist at other estrogen receptors (thus minimizing sidePartial agonist at other estrogen receptors (thus minimizing side
effects due to estrogen deprivation) - bone, uterus, liver andeffects due to estrogen deprivation) - bone, uterus, liver and
pituitarypituitary

Hot flushes – antiestrogenic actionHot flushes – antiestrogenic action

Decrease in LDL level but no change in HDL levelDecrease in LDL level but no change in HDL level

Improvement in bone mass and lipid profileImprovement in bone mass and lipid profile
 Kinetics: Absorbed orally and has biphasic half life – 10Kinetics: Absorbed orally and has biphasic half life – 10
Hrs and 7 days – long duration of actionHrs and 7 days – long duration of action

Excreted in BileExcreted in Bile

Dose is 10 to 20 mg BDDose is 10 to 20 mg BD

46. Tamoxifen – contd.Tamoxifen – contd.
 Uses:Uses:

Breast carcinoma of pre and post menopauseBreast carcinoma of pre and post menopause

Adjuvant therapy in early casesAdjuvant therapy in early cases

Palliative therapyPalliative therapy
 Side effects.Side effects.

The drug has a low incidence of adverse reactionsThe drug has a low incidence of adverse reactions

Hot flashes, nausea, vomiting, rash, menstrual irregularities andHot flashes, nausea, vomiting, rash, menstrual irregularities and
bleeding, infrequent depression, headache, hypercalcemia,bleeding, infrequent depression, headache, hypercalcemia,
edema, and blood dyscrasiasedema, and blood dyscrasias

Less toxic than anticancer drugsLess toxic than anticancer drugs
 Other SERM –Other SERM – Raloxifene, ormeloxifene etc.Raloxifene, ormeloxifene etc.

Raloxifene is estrogen antagonist of breast and endometriumRaloxifene is estrogen antagonist of breast and endometrium
while partial agonist of bone and CVSwhile partial agonist of bone and CVS
CH2CH3
O(CH3)2N-CH2-CH2
TAMOXIFEN (NOLVADEX)

47. Aromatase InhibitorsAromatase Inhibitors
 Letrozole, Anastrozole and ExemestaneLetrozole, Anastrozole and Exemestane
 MOA: LetrozoleMOA: Letrozole

Non steroidal compound, reversible inhibition ofNon steroidal compound, reversible inhibition of
aromatization all over the bodyaromatization all over the body

Suppression of proliferation of estrogen dependantSuppression of proliferation of estrogen dependant
breast carcinoma cellsbreast carcinoma cells

Rapid oral absorption – 100% bioavailability, large Vd,Rapid oral absorption – 100% bioavailability, large Vd,
t1/2 – 40 Hrst1/2 – 40 Hrs
 Uses: Early breast carcinoma and AdvancedUses: Early breast carcinoma and Advanced
breast carcinomabreast carcinoma

48. Progestins

49. PreparationsPreparations
 Progesterone Derivatives:Progesterone Derivatives:

Progesterone, Hydroxyprogesterone Caproate,Progesterone, Hydroxyprogesterone Caproate,
Medroxyprogesterone acet, Megesterol acetateMedroxyprogesterone acet, Megesterol acetate
 19-Nortestosterone derivatives:19-Nortestosterone derivatives:

Norethindrone, Norethynodrel, Lynestrenol,Norethindrone, Norethynodrel, Lynestrenol,
AllylestrenolAllylestrenol
 33rdrd
Generation compounds (Gonanes):Generation compounds (Gonanes):

norgestimate, norgestrel, desogestrel andnorgestimate, norgestrel, desogestrel and
levonogestrellevonogestrel
 Micronized formulations – for oral useMicronized formulations – for oral use

50. Actions of ProgesteroneActions of Progesterone
Uterus:Uterus:
 Responsible for Luteal phase of endometriumResponsible for Luteal phase of endometrium
 High level (pregnancy and luteal phase)High level (pregnancy and luteal phase)
prevents secretion of gonadotrophinsprevents secretion of gonadotrophins
 Maintenance of pregnancy – nidation andMaintenance of pregnancy – nidation and
maintenance of pregnancymaintenance of pregnancy

Decrease uterine motilityDecrease uterine motility

Depression of T-cell function and CMIDepression of T-cell function and CMI
 MenstruationMenstruation

51. Actions – contd.Actions – contd.
 Cervix:Cervix: viscid and cellular secretion – no sperm penetrationviscid and cellular secretion – no sperm penetration
 Vagina:Vagina: Pregnancy like changes – leucocyte infiltration andPregnancy like changes – leucocyte infiltration and
cornified epitheliumcornified epithelium
 Breast:Breast: Proliferation of acini in mammary glandsProliferation of acini in mammary glands

Prepares breast for lactation together with estrogenPrepares breast for lactation together with estrogen
 Metabolism:Metabolism:

impairment of glucose toleranceimpairment of glucose tolerance

Counteraction of benefits of oestrogensCounteraction of benefits of oestrogens
 CNS:CNS: SedationSedation
 Respiration:Respiration: StimulationStimulation
 Body temperature:Body temperature: rise in temperaturerise in temperature
 Pituitary:Pituitary: Weak Gn inhibitor, suppresses ovulation if given duringWeak Gn inhibitor, suppresses ovulation if given during
follicular phasefollicular phase

52. Progesterone – contd.Progesterone – contd.
 MOA:MOA:

Receptors are confined to female genital tracts,Receptors are confined to female genital tracts,
breasts and CNSbreasts and CNS

PRs are present in nucleus of target cellsPRs are present in nucleus of target cells

PR exists in 2 forms – PR-A and PR-B isoformsPR exists in 2 forms – PR-A and PR-B isoforms
(differing activities)(differing activities)
 Kinetics:Kinetics:

Inactive orally, high first pass metabolismInactive orally, high first pass metabolism

Synthetics are active orally and metbolized slowlySynthetics are active orally and metbolized slowly

Half-life of 8-24 HRsHalf-life of 8-24 HRs

53. Uses of ProgestinsUses of Progestins
 ContraceptiveContraceptive
 Hormonl replcement therapyHormonl replcement therapy
 Dysfunctional Uterine Bleeding: anovulatoryDysfunctional Uterine Bleeding: anovulatory
cyclescycles
 Endometriosis: anovulatory hypoestrogenic stateEndometriosis: anovulatory hypoestrogenic state
is created by progesteroneis created by progesterone
 Premenstrual syndromePremenstrual syndrome
 Threatened and habitual abortionThreatened and habitual abortion
 Endometrial carcinomaEndometrial carcinoma

54. Adverse EffectsAdverse Effects
Breast engorgement, headache, rise in body temp.,Breast engorgement, headache, rise in body temp.,
oedema, acne & mood swingsoedema, acne & mood swings
 Masculinization of external genitalia in the foetusMasculinization of external genitalia in the foetus
 Increased incidences of congenital abnormalitiesIncreased incidences of congenital abnormalities
 Irregular bleeding or amenorrheaIrregular bleeding or amenorrhea
 Lower HDL (19-nortestosterone derivatives)Lower HDL (19-nortestosterone derivatives)
 HyperglycaemiaHyperglycaemia

55. Antiprogestin - MifepristoneAntiprogestin - Mifepristone
 19-norsteroid compound – antiprogestational,19-norsteroid compound – antiprogestational,
antiglucocorticoid and antiandrogenic actionantiglucocorticoid and antiandrogenic action
Actions:Actions:
 Follicular phase: attenuation of Gn discharge – slowFollicular phase: attenuation of Gn discharge – slow
follicular development, failure of ovulationfollicular development, failure of ovulation
 Luteal phase: prevents secretory changes brought aboutLuteal phase: prevents secretory changes brought about
by progesteroneby progesterone
 Late cycle: Blocking of Progesterone action, increasedLate cycle: Blocking of Progesterone action, increased
PG release – uterine contractionPG release – uterine contraction
 Sensitization of endometrium to PG – menstruationSensitization of endometrium to PG – menstruation
 On Implantation: Blocking of decidution and dislodging ofOn Implantation: Blocking of decidution and dislodging of
conceptusconceptus
 In Menopause – progestational activityIn Menopause – progestational activity

56. Mifepristone – contd.Mifepristone – contd.
Kinetics:Kinetics: Absorbed orally and bioavailability is onlyAbsorbed orally and bioavailability is only
25% and half-life is 20-36 hrs25% and half-life is 20-36 hrs

CYP3A4CYP3A4
Uses:Uses:
1.1. Termination of PregnancyTermination of Pregnancy
2.2. Cervical primingCervical priming
3.3. Postcoital contraceptivePostcoital contraceptive
4.4. Induction of labour: single dose 2 days afterInduction of labour: single dose 2 days after
midcyclemidcycle
5.5. Cushing SyndromeCushing Syndrome
– Preparations: Tablet – 200 mgPreparations: Tablet – 200 mg

57. Pharmacology of HormonalPharmacology of Hormonal
ContraceptionContraception

58. Methods of ContraceptionMethods of Contraception
 Direct inhibition of spermatogenesisDirect inhibition of spermatogenesis
 Indirect inhibition of spermatogenesisIndirect inhibition of spermatogenesis
 Immunological techniques (vaccine)Immunological techniques (vaccine)
 Inhibition of ovulation (Hormonal contraceptives)Inhibition of ovulation (Hormonal contraceptives)
 Prevention of fertilizationPrevention of fertilization
 Anti-zygotic drugsAnti-zygotic drugs
 Inhibition of implantationInhibition of implantation
 use of spermicidal in vaginause of spermicidal in vagina
 IUCDIUCD

59. Female ContraceptionFemale Contraception
OralOral
 Combined pillCombined pill
 Sequential pillSequential pill
 Phased regimenPhased regimen
 Mini pillMini pill
 Post-coital pillPost-coital pill
InjectableInjectable
 Long actingLong acting

progesteroneprogesterone
alonealone
 Long actingLong acting

progesterone +progesterone +
estrogenestrogen
 Implants:Implants:

NorplantNorplant

60. HistoryHistory
 The oral contraceptive pill (combined OC) was firstThe oral contraceptive pill (combined OC) was first
introduced in 1960introduced in 1960
 1970: Introduction low dose or second generation of1970: Introduction low dose or second generation of
OCSOCS
 1980: biphasic or triphasic regimens1980: biphasic or triphasic regimens
 1990: 3rd generation OCS1990: 3rd generation OCS
(O + P has less androgenic activity,(O + P has less androgenic activity,
e.g, norgestimate 0.25mg or desogestrel 0.15 mg)e.g, norgestimate 0.25mg or desogestrel 0.15 mg)
 Since then it has undergone many modifications and hasSince then it has undergone many modifications and has
been used by millions of women worldwide.been used by millions of women worldwide.

61. Combined PillCombined Pill
 Low-dose oral contraceptives: productsLow-dose oral contraceptives: products
containing less than 50ug ethinyl estradiolcontaining less than 50ug ethinyl estradiol
 First generation oral contraceptives:First generation oral contraceptives:
products containing 50ug or more of ethinyl estradiolproducts containing 50ug or more of ethinyl estradiol
 Second generation oral contraceptives:Second generation oral contraceptives:
products containing levonorgestrel, norgestimate andproducts containing levonorgestrel, norgestimate and
other members of northindrone family and 30 or 40ugother members of northindrone family and 30 or 40ug
ethinyl estradiolethinyl estradiol
 Third generation oral contraceptives:Third generation oral contraceptives:
products containing desogestrel or gestodene with 20 orproducts containing desogestrel or gestodene with 20 or
30ug ethinyl estradiol30ug ethinyl estradiol

Newer progestins (gestodene and desogestrel) have beenNewer progestins (gestodene and desogestrel) have been
shown to have little or no androgenic activityshown to have little or no androgenic activity

62. FormulationsFormulations
 Formulations may be :Formulations may be :
1.1. MonophasicMonophasic (each tablet contains a fixed(each tablet contains a fixed
amount of estrogen and progestin);amount of estrogen and progestin);
2.2. BiphasicBiphasic (each tablet contains a fixed amount(each tablet contains a fixed amount
of estrogen, while the amount of progestinof estrogen, while the amount of progestin
increases in the second half of the cycle); orincreases in the second half of the cycle); or
3.3. TriphasicTriphasic (the amount of estrogen may be fixed(the amount of estrogen may be fixed
or variable, while the amount of progestinor variable, while the amount of progestin
increases in 3 equal phases).increases in 3 equal phases).

63. FormulationsFormulations
 Biphasic and triphasicBiphasic and triphasic formulations were initiallyformulations were initially
developed with the intent of lowering the total steroiddeveloped with the intent of lowering the total steroid
content of combined OCs (estrogen – 30 to 40 mcg)content of combined OCs (estrogen – 30 to 40 mcg)
 Two types of estrogen are used in combined OCs:Two types of estrogen are used in combined OCs:
ethinyl estradiol and mestranolethinyl estradiol and mestranol
 Mestranol is aMestranol is a “prodrug”“prodrug” that is converted in vivo tothat is converted in vivo to
ethinyl estradiolethinyl estradiol
 Several different progestins, of varying degrees ofSeveral different progestins, of varying degrees of
progestational potency, are used in combined OCsprogestational potency, are used in combined OCs

64. Phased Regimens: ExamplesPhased Regimens: Examples
Biphasic:Biphasic:
10 (O+P) + 11 (O+PP) + 7 (DF)10 (O+P) + 11 (O+PP) + 7 (DF)
Triphasic:Triphasic:
I 6 (E.O 30 µg + Levonorg. 50 µg)I 6 (E.O 30 µg + Levonorg. 50 µg)
II 5 (E.O 40 µg + Levonorg. 75 µg)II 5 (E.O 40 µg + Levonorg. 75 µg)
III 10 (E.O 30 µg + Levonorg. 125 µg)III 10 (E.O 30 µg + Levonorg. 125 µg)
Combined preparations:Combined preparations:
21 days (O+P) + 7 days (DF)21 days (O+P) + 7 days (DF)
99 – 100% effective99 – 100% effective

65. MinipillMinipill
 Progesterone only pillProgesterone only pill
 To eliminate estrogen to avoid long termTo eliminate estrogen to avoid long term
risks of estrogenrisks of estrogen
 Low dose estrogen is taken daily withoutLow dose estrogen is taken daily without
gapgap
 Efficacy is 96-98%Efficacy is 96-98%

66. Postcoital (Emergency)Postcoital (Emergency)
 Levonorgestrel 0.5 mg + EE 0.1 mg –Levonorgestrel 0.5 mg + EE 0.1 mg –
ovralovral tablettablet
 Levonorgestrel (0.75 mg) alone – 12 HrLevonorgestrel (0.75 mg) alone – 12 Hr
apartapart
 Mifepristone – 400 mg (2 tablets)Mifepristone – 400 mg (2 tablets)

67. InjectableInjectable
 Long acting Progestin aloneLong acting Progestin alone
1.1. Depot medroxyprogesterone (DMPA) – 150Depot medroxyprogesterone (DMPA) – 150
mg (1 ml vial) – half life – 50 days)mg (1 ml vial) – half life – 50 days)
2.2. Norethidrone (Norethisterone) – 200 mg (1Norethidrone (Norethisterone) – 200 mg (1
ml vial) – repeat at 2 monthsml vial) – repeat at 2 months
 Long acting progestin + estrogen:Long acting progestin + estrogen:

Medroxyprogesterone + estradol cypionate –Medroxyprogesterone + estradol cypionate –
IM injection – monthlyIM injection – monthly
 Implants – norplants, progestesert etc.Implants – norplants, progestesert etc.

68. Missed Pill AdviseMissed Pill Advise
 If 1 or 2 of 30-35mcg ethinylestradiol pill or 1 of 20If 1 or 2 of 30-35mcg ethinylestradiol pill or 1 of 20
mcgmcg

Advise to take the most recent pill as soon as remembers,Advise to take the most recent pill as soon as remembers,
continue taking remaining pill at usual time, she does not requirecontinue taking remaining pill at usual time, she does not require
additional contraception or emergency contraceptionadditional contraception or emergency contraception
 If 3 or more of 30-35 or 2 or more 20 mcgIf 3 or more of 30-35 or 2 or more 20 mcg

Advise as above, but to use extra method of contraception untilAdvise as above, but to use extra method of contraception until
pills have been taken for 7 days in a rowpills have been taken for 7 days in a row

If pill is missed in week 1 ( days1-7)and unprotected sexualIf pill is missed in week 1 ( days1-7)and unprotected sexual
intercourse has taken place in pill free week or wk 1 thenintercourse has taken place in pill free week or wk 1 then
emergency contraception is neededemergency contraception is needed

If pills missed in wk 3 ( days 15-21), advise to finish pill in packIf pills missed in wk 3 ( days 15-21), advise to finish pill in pack
and start new pack the next day, omitting pill free intervaland start new pack the next day, omitting pill free interval

If one has missed > 7 consecutive days then consider asIf one has missed > 7 consecutive days then consider as
stopped COCPstopped COCP

69. Mechanism of actionMechanism of action
 Combination pill, given daily for 3 of every 4Combination pill, given daily for 3 of every 4
weeks:weeks:

Prevents ovulation by inhibiting gonadotropinPrevents ovulation by inhibiting gonadotropin
secretion via effect on both pituitary andsecretion via effect on both pituitary and
hypothalamic centershypothalamic centers

Progestational agent in pill ; suppresses LHProgestational agent in pill ; suppresses LH
secretion(thus prevents ovulation)secretion(thus prevents ovulation)

Estrogenic agent ; suppresses FSH secretion (thusEstrogenic agent ; suppresses FSH secretion (thus
prevents selection and emergence of dominantprevents selection and emergence of dominant
follicle)follicle)

Progestin only preparations – suppresses LH surgeProgestin only preparations – suppresses LH surge
and also by direct actionand also by direct action

70. Mechanism of action – contd.Mechanism of action – contd.
 Thick Cervical mucus secretion makingThick Cervical mucus secretion making
hostile for sperm penetrationhostile for sperm penetration
 Failure of implantation – hyperproliferativeFailure of implantation – hyperproliferative
and hypersecretory endometriumand hypersecretory endometrium
 Uterine and tubal contraction – peristalsisUterine and tubal contraction – peristalsis
within the fallopian tubewithin the fallopian tube
 Dislodging of implanted blastocyteDislodging of implanted blastocyte

71. Adverse EffectsAdverse Effects
 Some combined OC users will experience minor side-Some combined OC users will experience minor side-
effects, most commonly during the first 3 cycles.effects, most commonly during the first 3 cycles.
 These side-effects may lead to discontinuation of theThese side-effects may lead to discontinuation of the
combined OCcombined OC
 The most common reason patients discontinueThe most common reason patients discontinue
combined OC use is:combined OC use is:
1.1. Abnormal menstrual bleeding, followed by :Abnormal menstrual bleeding, followed by :
2.2. Nausea,Nausea,
3.3. Weight gain,Weight gain,
4.4. Mood changes,Mood changes,
5.5. Breast tendernessBreast tenderness
6.6. Headache.Headache.

72. Adverse Effects - LateAdverse Effects - Late
 ChloasmaChloasma
 Pruritus vulvaePruritus vulvae
 Carbohydrate intoleranceCarbohydrate intolerance
 Mood swingsMood swings

73. Serious ComplicationsSerious Complications
 Leg vein and pulmonary thrombosisLeg vein and pulmonary thrombosis
 Coronary and cerebral thrombosisCoronary and cerebral thrombosis
 HypertensionHypertension
 Genital carcinomaGenital carcinoma
 Benign hepatomasBenign hepatomas
 GallstonesGallstones

74. Contraindications (WHO)Contraindications (WHO)
1.1. < 6 weeks postpartum if breastfeeding< 6 weeks postpartum if breastfeeding
2.2. Smoker over the age of 35 (≥ 15 cigarettes per day)Smoker over the age of 35 (≥ 15 cigarettes per day)
3.3. Hypertension (systolic ≥ 160mm Hg or diastolic ≥ 100mm Hg)Hypertension (systolic ≥ 160mm Hg or diastolic ≥ 100mm Hg)
4.4. Current or past history of venous thromboembolism (VTE)Current or past history of venous thromboembolism (VTE)
5.5. Ischemic heart diseaseIschemic heart disease
6.6. History of cerebrovascular accidentHistory of cerebrovascular accident
7.7. Complicated valvular heart diseaseComplicated valvular heart disease
8.8. Migraine headacheMigraine headache
9.9. Breast cancer (current)Breast cancer (current)
10.10. Diabetes with retinopathy/nephropathy/neuropathyDiabetes with retinopathy/nephropathy/neuropathy
11.11. CirrhosisCirrhosis
12.12. Liver tumour (adenoma or hepatoma)Liver tumour (adenoma or hepatoma)

75. Relative ContraindicationsRelative Contraindications
1.1. Smoker over the age of 35 (< 15 cigarettes per day)Smoker over the age of 35 (< 15 cigarettes per day)
2.2. Adequately controlled hypertensionAdequately controlled hypertension
3.3. Hypertension (systolic 140–159mm Hg,Hypertension (systolic 140–159mm Hg,
diastolic 90–99mm Hg)diastolic 90–99mm Hg)
4.4. Migraine headache over the age of 35Migraine headache over the age of 35
5.5. Currently symptomatic gallbladder diseaseCurrently symptomatic gallbladder disease
6.6. History of combined OC-related cholestasisHistory of combined OC-related cholestasis
7.7. Mentally illMentally ill
8.8. Undiagnosed vaginal BleedingUndiagnosed vaginal Bleeding
Centchroman and male contraceptiveCentchroman and male contraceptive

76. Remember !Remember !
 Pharmacological actions of testosterone, mechanism ofPharmacological actions of testosterone, mechanism of
action, adverse effects and therapeutic usesaction, adverse effects and therapeutic uses
 Danazol, Flutamide and Finasteride detailsDanazol, Flutamide and Finasteride details
 Anabolic SteroidsAnabolic Steroids
 Actions of Oestrogens and usesActions of Oestrogens and uses
 Clomiphene citrate in detailClomiphene citrate in detail
 Antiprogestin – MifepristoneAntiprogestin – Mifepristone
 Different contraceptive measureDifferent contraceptive measure
 Different Hormonal contraceptivesDifferent Hormonal contraceptives
 Mechanism of action, adverse effects andMechanism of action, adverse effects and
contraindications of OCPscontraindications of OCPs

77. THANK YOUTHANK YOU