gonadal drugs ma. janetth b. serrano, m.d., dpba

GONADAL GONADAL DRUGSDRUGS

Ma. Janetth B. Serrano, M.D., DPBAMa. Janetth B. Serrano, M.D., DPBA

Gonads: Gonads: OvaryOvary

Quiescent during rapid growth & maturation Quiescent during rapid growth & maturation

At puberty:At puberty:

- Gonadarche- Gonadarche →→ beginning of ovarian function beginning of ovarian function

- Menstrual cycle- Menstrual cycle

→ → a 30- to 40- year period of cyclic functiona 30- to 40- year period of cyclic function

→→ manifested as regular episodes of manifested as regular episodes of bleedingbleeding

- Menopause- Menopause

→→ if ovaries fail to respond to if ovaries fail to respond to gonadotropins gonadotropins secreted by the ant. pituitary.secreted by the ant. pituitary.

HypothalamusHypothalamus↓↓

GnRHGnRH ↓↓

AAnterior Pituitarynterior Pituitary↓↓

FSH / LHFSH / LH↓↓

Ovary / TestesOvary / Testes

Estrogen/ Testosterone/Estrogen/ Testosterone/ Progestins AndrogensProgestins Androgens

NEUROENDOCRINE CONTROL OF THE NEUROENDOCRINE CONTROL OF THE MENSTRUAL CYCLEMENSTRUAL CYCLE


(-)

(-)


DISTURBANCES IN OVARIAN FUNCTION:DISTURBANCES IN OVARIAN FUNCTION: environmental or emotional stressenvironmental or emotional stress anovulatory cycles: anovulatory cycles:

eating disorders (bulimia,anorexia)eating disorders (bulimia,anorexia) severe exercisesevere exercise

organic causes:organic causes: pituitary prolactinomaspituitary prolactinomas ovary gives rise to: ovary gives rise to: androgen producing neoplasms (arrhenoblastoma, androgen producing neoplasms (arrhenoblastoma,

Leydig cell tumors, estrogen producing granulosa Leydig cell tumors, estrogen producing granulosa cell tumors)cell tumors)

minor causes: minor causes: inflammatory or neoplastic inflammatory or neoplastic processes that inluence function of the ovaries, uterus processes that inluence function of the ovaries, uterus or pituitaryor pituitary

EstrogEstrogensens

Naturally occuring:

17β – estradiol (most potent) Estrone Estriol

Synthetic Steroidal:

Ethinyl estradiol Mestranol Quinestrol Equilin

Synthetic Nonsteroidal:

Diethylstilbesterol Chlorotrianesene Methallenestril Methestrol Dienestrol Benzestrel Hexistrol Genistein

Immediate precursors: Immediate precursors:

Androstenedione / TestosteroneAndrostenedione / Testosterone Ovaries – principal source of circulating estrogenOvaries – principal source of circulating estrogen Other sources: Other sources:

liver (estrone, estriol fr. estrsdiol)liver (estrone, estriol fr. estrsdiol) Peripheral tissues (fr. androstenedione & other Peripheral tissues (fr. androstenedione & other

androgens)androgens) Pregnancy: fetoplacental unit ( fetal adrenal zone, Pregnancy: fetoplacental unit ( fetal adrenal zone,

secreting androgen precursor, placenta)secreting androgen precursor, placenta) Stallion – equilenin and equilinStallion – equilenin and equilin Soybeans - flavinoidsSoybeans - flavinoids

EstrogeEstrogensns

binds strongly to SHBG and less to albuminbinds strongly to SHBG and less to albumin

estrdiol converted by the liver to:estrdiol converted by the liver to: estrone & estriolestrone & estriol 2-hydroxylated derivatives 2-hydroxylated derivatives conjugated metabolites catechol estrogens conjugated metabolites catechol estrogens

may serve as neurotransmitters in the CNSmay serve as neurotransmitters in the CNS

converted by COM-T to 2- and 4- methoxy converted by COM-T to 2- and 4- methoxy compoundscompounds

excreted in the bile; small amounts in excreted in the bile; small amounts in breastmilkbreastmilk

EstrogeEstrogensnsPHARMACOKINETICSPHARMACOKINETICS

Biosynthetic Pathway for Biosynthetic Pathway for Estrogens:Estrogens:

Dehydroepi- Dehydroepi- 16 16 αα-OHase-OHase 16 16αα-Hydroxyde--Hydroxyde- 1616αα--Hydroxydehy - Hydroxydehy - androsteroneandrosterone hydroepiandros hydroepiandros hydroepiandros-hydroepiandros- terone terone terone terone

AndrostenedioneAndrostenedione aromatase aromatase Estrone Estrone EstriolEstriol

TESTOSTERONE TESTOSTERONE aromatasearomatase ESTRADIOL ESTRADIOL

primarily by regulating gene primarily by regulating gene expressionexpression

SHBG-bound estrogens SHBG-bound estrogens dissociate & dissociate & enter cell enter cell bind to their receptor bind to their receptor

Receptor-hormone complex Receptor-hormone complex bind to bind to Estrogen Response Elements or ERE’s Estrogen Response Elements or ERE’s (specific sequence of nucleotides) (specific sequence of nucleotides)

EstrogenEstrogenssMECHANISM OF MECHANISM OF

ACTIONACTION

1. 1. Female maturationFemale maturation required for 2 required for 2 OO sexual characteristics: sexual characteristics:

stimulate development of stimulate development of vagina, uterus & vagina, uterus & tubestubes

breast breast development development stromal development, stromal development, ductal growth and accretion of fatductal growth and accretion of fat

accelerated growth phase and closure of accelerated growth phase and closure of epiphysisepiphysis

axillary and pubic axillary and pubic hairhair regional regional pigmentationpigmentation of axilla, areola & genital of axilla, areola & genital

areaarea

EstrogeEstrogensns

PHYSIOLOGIC PHYSIOLOGIC EFFECTSEFFECTS

2. 2. Endometrial effectsEndometrial effects hyperplasia of the endometrium hyperplasia of the endometrium continuous continuous

exposureexposure

3. 3. Metabolic and Cardiovascular effects:Metabolic and Cardiovascular effects: Lipoprotein: Lipoprotein: HDL , slight HDL , slight LDL LDL plasma cholesterolplasma cholesterol plasma triglyceridesplasma triglycerides

4. 4. Blood CoagulationBlood Coagulation enhance coagulabilityenhance coagulability Factors II, Vii, IX, XFactors II, Vii, IX, X antithrombin IIIantithrombin III plasminogen level plasminogen level platelet adhesiveness platelet adhesiveness

EstrogeEstrogensnsPHYSIOLOGIC PHYSIOLOGIC

EFFECTSEFFECTS

1.1. Primary hypogonadismPrimary hypogonadism associated with hypopituitarismassociated with hypopituitarism Turner’s syndromeTurner’s syndrome – ovarian dysgenesis with – ovarian dysgenesis with

dwarfismdwarfism treatment begins at puberty – 11 to 13 years:treatment begins at puberty – 11 to 13 years:

to stimulate development of 2to stimulate development of 2OO sexual sexual characteristics and mensescharacteristics and menses

to prevent osteoporosisto prevent osteoporosis to avoid physiologic consequenses of delayed to avoid physiologic consequenses of delayed

puberty and estrogen deficiencypuberty and estrogen deficiency

Dosage:Dosage:Conjugated estrogen 0.3 mgConjugated estrogen 0.3 mg or or Ethinyl estradiol 5-Ethinyl estradiol 5-10ug10ug

on days 1 to 21 of each monthon days 1 to 21 of each month when growth is completed when growth is completed Chronic Tp with Chronic Tp with

estrogen and progestinsestrogen and progestins

EstrogeEstrogensnsCLINICAL USESCLINICAL USES

2. Postmenopausal Hormone Replacement 2. Postmenopausal Hormone Replacement TherapyTherapy

major indicationmajor indication prevent bone loss (osteoporosis) prevent bone loss (osteoporosis) decrease vasomotor symptoms decrease vasomotor symptoms prevention of cardiovascular disease prevention of cardiovascular disease prevent vaginitisprevent vaginitis Dosage: Dosage:

Conjugated EstrogenConjugated Estrogen – 0.3 to 1.25 ug/day – 0.3 to 1.25 ug/dayEthinyl EstradiolEthinyl Estradiol – 0.01 to 0.02 mg/day – 0.01 to 0.02 mg/day


Replacement RegimenReplacement Regimen::

A: Sequential hormone administrationA: Sequential hormone administration 1. Estrogen for first 25 days1. Estrogen for first 25 days 2. MPA (Medroxyprogesterone acetate) 10 mg/day for 2. MPA (Medroxyprogesterone acetate) 10 mg/day for

the last 10 to 14 days of estrogen therapythe last 10 to 14 days of estrogen therapy 3. No hormone treatment for 5 to 6 days 3. No hormone treatment for 5 to 6 days (+) withdrawal (+) withdrawal

bleedingbleeding

B: “Continuous” hormone administrationB: “Continuous” hormone administration1. estrogen 0.625 mg given continuously on a daily basis1. estrogen 0.625 mg given continuously on a daily basis2. progestin MPA 2.5 to 5 mg jointly given during the first 2. progestin MPA 2.5 to 5 mg jointly given during the first

10 to 13 days of each month10 to 13 days of each month3. 3. no cyclic bleedingno cyclic bleeding

PROGESTINS – included to decrease endometrial PROGESTINS – included to decrease endometrial hyperplasia and incidence of endometrial hyperplasia and incidence of endometrial carcinomacarcinoma


3. Contraception3. Contraception major indicationmajor indication

4. OTHER USES:4. OTHER USES: DUB & intractable dysmenorrhea DUB & intractable dysmenorrhea

(Es + Progestins) (Es + Progestins) Hirsutism & amenorrhea Hirsutism & amenorrhea DES DES prostate carcinoma prostate carcinoma Severe cystic acneSevere cystic acne


postmenopausal bleedingpostmenopausal bleeding carcinogenic action – breast, carcinogenic action – breast,

endometrialendometrial thromboembolic disease, HPNthromboembolic disease, HPN GB disease, cholestasisGB disease, cholestasis Nausea & breast tendernessNausea & breast tenderness MigrainesMigraines Changes in moodChanges in mood

EstrogeEstrogensnsADVERSE ADVERSE

EFFECTSEFFECTS

CONTRAINDICATIONS:CONTRAINDICATIONS:

estrogen- dependent neoplasmsestrogen- dependent neoplasms

undiagnosed genital bleedingundiagnosed genital bleeding

history of liver diseasehistory of liver disease

history of thromboembolic disorderhistory of thromboembolic disorder

heavy smokersheavy smokers

EstrogeEstrogensnsCONTRAINDICATIONCONTRAINDICATION

SS

ANTI-ESTROGENS: ANTI-ESTROGENS: A. TamoxifenA. Tamoxifen

a competetive partial agonist inhibitor of a competetive partial agonist inhibitor of estradiol at estrogen receptorsestradiol at estrogen receptors

nonsteroidal agent given orallynonsteroidal agent given orally initial half-life: 7 to 14 hoursinitial half-life: 7 to 14 hours excretion: liverexcretion: liver Cl. Indication: palliative/adjuvant tp of breast Cl. Indication: palliative/adjuvant tp of breast

CACA Dosage: 10-20 mg BID orallyDosage: 10-20 mg BID orally Adverse effects: nausea & vomitingAdverse effects: nausea & vomiting

hot flasheshot flashesvaginal bleeding, menstrual irregularities, skin vaginal bleeding, menstrual irregularities, skin

rashrash risk of endometrial cancerrisk of endometrial cancer loss of lumbar spine bone density loss of lumbar spine bone density plasma lipid changes plasma lipid changes risk of atherosclerosis risk of atherosclerosis

Gonadal Gonadal InhibitorsInhibitors

Anti - Anti - EstrogensEstrogens

B. TOREMIFENEB. TOREMIFENE

C. RALOXIFENEC. RALOXIFENE ““selective estrogen receptor modulator”selective estrogen receptor modulator” high first pass effect, large Vdhigh first pass effect, large Vd long half-life: >24 hourslong half-life: >24 hours Cl. Indication: prevention of postmenopausal Cl. Indication: prevention of postmenopausal

osteoporosisosteoporosis

D. CLOMIPHENED. CLOMIPHENE competetive inhibitor of endogenous estrogencompetetive inhibitor of endogenous estrogen partial agonist at pituitary partial agonist at pituitary ovulation-inducing agentovulation-inducing agent



ESTROGEN SYNTHESIS INHIBITORSESTROGEN SYNTHESIS INHIBITORS1. GnRH1. GnRH

continuous administration prevents ovarian continuous administration prevents ovarian synthesis of estrogensynthesis of estrogen

2. AMINOGLUTETHIMIDE2. AMINOGLUTETHIMIDE inhibits aromatase activityinhibits aromatase activity

3. AROMATASE INHIBITORS3. AROMATASE INHIBITORSa. Testolactonea. Testolactone – weak inhibitor – weak inhibitor

b. Anastrozoleb. Anastrozoleselective nonsteroidal inhibitor of aromataseselective nonsteroidal inhibitor of aromataseeffective in tamoxifen-resistant breast tumorseffective in tamoxifen-resistant breast tumors

c. Letrozolec. Letrozole – similar to anastrozole – similar to anastrozoled. Exemestaned. Exemestane

steroid molecule that irreversibly inhibits steroid molecule that irreversibly inhibits aromatasearomatase

advanced breast CAadvanced breast CAe. Fadrozolee. Fadrozole – newer oral nonsteroidal – newer oral nonsteroidal



CLOMIPHENECLOMIPHENE Partial agonist at estrogen receptorsPartial agonist at estrogen receptors

MOA: MOA: secretion of gonadotropins & estrogens secretion of gonadotropins & estrogens by inhibiting estradiol’s negative feedback effectby inhibiting estradiol’s negative feedback effect

Effects: Effects: 1. stimulate ovulation in females with amenorrhea & 1. stimulate ovulation in females with amenorrhea &

other ovulatory disordersother ovulatory disorders2. blocks inhibitory influence of estrogen on the 2. blocks inhibitory influence of estrogen on the

hypothalamushypothalamus

Clinical Use:Clinical Use:1. Treatment of disorders of ovulation in patients wishing 1. Treatment of disorders of ovulation in patients wishing

to be pregnantto be pregnantno use in ovarian & pituitary failureno use in ovarian & pituitary failuresingle ovulation induced by a single course of single ovulation induced by a single course of

therapytherapy

Ovulation Ovulation Inducing AgentsInducing Agents

CLOMIPHENECLOMIPHENE Dosage: 50 mg/ d X 5 daysDosage: 50 mg/ d X 5 days

(+) ovulation (+) ovulation same course repeated until same course repeated until pregnancy occurspregnancy occurs

(-) ovulation (-) ovulation 100 mg/d X 5 days 100 mg/d X 5 days if (+) menses & if (+) menses & ovulation, start next course on 5th day of cycleovulation, start next course on 5th day of cycle

Adverse Effects:Adverse Effects: hot flushes – most commonhot flushes – most common eye symptoms – due to intensification & eye symptoms – due to intensification &

prolongation of after imagesprolongation of after images ovarian enlargementovarian enlargement multiple pregnancy – 10%multiple pregnancy – 10% rare: headache, constipation, allergic reactions, rare: headache, constipation, allergic reactions,

reversible hair lossreversible hair loss

C/I: patients with enlarged ovariesC/I: patients with enlarged ovaries > 1 year tx: assted with low-grade ovarian > 1 year tx: assted with low-grade ovarian

CACA

Ovulation Ovulation Inducing AgentsInducing Agents

Natural: Natural: PROGESTERONEPROGESTERONE

most important progestin in humansmost important progestin in humans

precursor to estrogens, androgens, precursor to estrogens, androgens, adrenocortical steroidsadrenocortical steroids

synthesized in the ovary (corpus synthesized in the ovary (corpus luteum), testis, adrenals, placentaluteum), testis, adrenals, placenta

ProgestiProgestinsns


Synthetic:Synthetic:

A. 21-Carbon compounds (Progestrone & A. 21-Carbon compounds (Progestrone & derivatives)derivatives)

HydroxyprogesteroneHydroxyprogesterone- longest DOA (8-14 days) - longest DOA (8-14 days)

MedroxyprogesteroneMedroxyprogesterone MegestrolMegestrol

B. 17-Ethinyl testosterone derivativesB. 17-Ethinyl testosterone derivatives DimethisteroneDimethisterone

C. 19-Nortestosterone derivatives C. 19-Nortestosterone derivatives

(3rd generation)(3rd generation)

1. Desogestrel1. Desogestrel 6. Norethindrone acetate6. Norethindrone acetate

2. Norethynodrel2. Norethynodrel 7. Ethynodiol acetate7. Ethynodiol acetate

3. Lynestrenol3. Lynestrenol 8. L-Norgestrel8. L-Norgestrel

4. Norethindrone4. Norethindrone 9. Gestodene9. Gestodene

5. Norgestimate5. Norgestimate

MECHANISM:MECHANISM:binds to progesterone receptorsbinds to progesterone receptors



Carbohydrate metabolismCarbohydrate metabolism insulin levelsinsulin levels insulin response to glucoseinsulin response to glucose promote glycogen storage in the promote glycogen storage in the

liverliver

favor fat depositionfavor fat deposition promote ketogenesispromote ketogenesis compete with aldosterone compete with aldosterone (( Na+ reabsorption) Na+ reabsorption)

PHYSIOLOGIC EFFECTSPHYSIOLOGIC EFFECTS

body temperaturebody temperature ventilatory response to CO2ventilatory response to CO2 depressant & hypnotic effectsdepressant & hypnotic effects

o Sexual characteristics:Sexual characteristics: breast: alveolobular devt. of the secretory breast: alveolobular devt. of the secretory

apparatusapparatus endometrium: maturation & secretory endometrium: maturation & secretory

changeschanges

o Important in the maintenance of pregnancyImportant in the maintenance of pregnancy plasma amino acid levels plasma amino acid levels urinary urinary

nitrogen excretionnitrogen excretion

ProgestiProgestinsnsPHYSIOLOGIC EFFECTSPHYSIOLOGIC EFFECTS

Synthetic progestins:Synthetic progestins:

no androgenic activity:no androgenic activity:desogestrel, desogestrel, norgestimate, norgestimate, gestodenegestodene


rapidly absorbedrapidly absorbed approx. half life: 5 minapprox. half life: 5 min stored in body fatsstored in body fats metabolite: Pregnanediolmetabolite: Pregnanediol Elimination: urine as Elimination: urine as

Pregnanediol glucoronatePregnanediol glucoronate

ProgestiProgestinsnsPHARMACOKINETICSPHARMACOKINETICS

Hormone replacement therapyHormone replacement therapyHormonal contraceptionHormonal contraceptionOvarian suppression:Ovarian suppression:

> dysmenorrhea> dysmenorrhea > hirsutism> hirsutismendometriosisendometriosis > uterine bleeding> uterine bleeding

Premenstrual syndrome Premenstrual syndrome progesterone & MPAProgestinsprogesterone & MPAProgestins

ProgestiProgestinsnsCLINICAL USESCLINICAL USES

Diagnostic testDiagnostic test Estrogen secretion Estrogen secretion Progesterone Progesterone 150 mg/d or MPA 10 150 mg/d or MPA 10

mg/d mg/d for 5-7 days for 5-7 days withdrawal withdrawal bleeding in amenorrheic patientsbleeding in amenorrheic patients

o Single drug:Single drug: MPAMPA 150 mg IM every 90 days 150 mg IM every 90 days

prolonged anovulation and prolonged anovulation and amenorrheaamenorrhea

MPAMPA 10-20 mg p.o. twice weekly or 10-20 mg p.o. twice weekly or 100 mg/m2 I.M. every 1-2 weeks 100 mg/m2 I.M. every 1-2 weeks prevent menstruationprevent menstruation

ProgestiProgestinsnsCLINICAL USESCLINICAL USES

BPBP

HDL HDL androgenic progestins androgenic progestins

ProgestiProgestinsnsADVERSE EFFECTSADVERSE EFFECTS

1. ANDROGENS1. ANDROGENS testosterone, androstenedione, testosterone, androstenedione,

dehydroepiandrosteronedehydroepiandrosterone responsible for hair growth, stimulation of responsible for hair growth, stimulation of

libido, metabolic effectslibido, metabolic effects asstd. with hirsutism & amenorrheaasstd. with hirsutism & amenorrhea

2. INHIBIN and ACTIVIN2. INHIBIN and ACTIVIN dimer (inhibin) dimer (inhibin) inhibits FSH secretion inhibits FSH secretion dimer (activin) dimer (activin) FSH secretion FSH secretion

Other Ovarian Other Ovarian HormonesHormones

3. RELAXIN3. RELAXIN found in the ovary, placenta, uterusfound in the ovary, placenta, uterus glycogen storage and water uptakeglycogen storage and water uptake facilitates dilatation & shortens laborfacilitates dilatation & shortens labor

4. Non steroidal substances4. Non steroidal substances corticotropin-releasing hormone, corticotropin-releasing hormone,

follistatin, PGfollistatin, PG with paracrine effects within the ovarywith paracrine effects within the ovary

Other Ovarian Other Ovarian HormonesHormones

1. MIFEPRISTONE (RU486)1. MIFEPRISTONE (RU486) a derivative of ‘19-nor progestin a derivative of ‘19-nor progestin

norethindrone’norethindrone’ a potent competetive antagonist of a potent competetive antagonist of

progesterone and glucocorticoid at their progesterone and glucocorticoid at their receptorsreceptors

acts as partial agonist if progestin is absentacts as partial agonist if progestin is absent (+) luteolytic in women at midluteal period(+) luteolytic in women at midluteal period Pharmacokinetics:Pharmacokinetics:

oral route with good bioavailabilityoral route with good bioavailabilityplasma half-life: 20 to 40 hoursplasma half-life: 20 to 40 hourshepatic metabolismhepatic metabolismelimination: feceselimination: feces


Anti - Anti - ProgestinsProgestins

MIFEPRISTONEMIFEPRISTONE Therapeutic indications:Therapeutic indications:

1. Medical abortion during the first trimester1. Medical abortion during the first trimester dosage: dosage:

400-600mg/day X 4 days or 800 mg/day X 2 days + 400-600mg/day X 4 days or 800 mg/day X 2 days + ProstaglandinProstaglandin 48 hrs after antiprogestin to 48 hrs after antiprogestin to myometrial contraction & ensure expulsion of detached myometrial contraction & ensure expulsion of detached blastocystblastocyst

major adverse effect: major adverse effect: prolonged bleedingprolonged bleeding

combination: combination: 600 mg o.d. SD + 600 mg o.d. SD + PG E1PG E1 vaginal pessary or 1 gm. vaginal pessary or 1 gm.

Misoprostol Misoprostol (95% effective during 1st 7 weeks post (95% effective during 1st 7 weeks post conception)conception)

adverse effects: vomiting, diarrhea, abdominal pain, adverse effects: vomiting, diarrhea, abdominal pain, pelvic painpelvic pain



MIFEPRISTONEMIFEPRISTONETherapeutic indications:Therapeutic indications:

2. Postcoital contraceptive2. Postcoital contraceptive prevents implantationprevents implantation dosage: 600 mg SDdosage: 600 mg SD

3. Induction of labor after fetal death & 3. Induction of labor after fetal death & at the end of 3rd trimesterat the end of 3rd trimester

4. Tx of endometriosis, leiomyoma, 4. Tx of endometriosis, leiomyoma, breast cancer, meningiomasbreast cancer, meningiomas



DANAZOLDANAZOL an isoxazole derivative of ethisteronean isoxazole derivative of ethisterone

weak agonist at progestational, androgenic weak agonist at progestational, androgenic and glucocorticoid receptorsand glucocorticoid receptors

inhibitor of gonadal functioninhibitor of gonadal function

MOA: binds to receptors MOA: binds to receptors initiate androgen- initiate androgen-specific RNA synthesisspecific RNA synthesis

Major metabnolite: ETHISTERONE –with Major metabnolite: ETHISTERONE –with progestational & androgenic effectsprogestational & androgenic effects

t ½t ½ = >15 hrs = >15 hrs

Elimination: urine & fecesElimination: urine & feces



DANAZOLDANAZOL

Clinical Uses:Clinical Uses: treatment of endometriosistreatment of endometriosis

600 mg/d reduced to 400 mg/d after 1 mo. 600 mg/d reduced to 400 mg/d after 1 mo. then 200 mg/d after 2 mos (85% with then 200 mg/d after 2 mos (85% with improvement in 3-12 mos)improvement in 3-12 mos)

fibrocystic disease of the breastfibrocystic disease of the breast

hematologic or allergic disorders:hematologic or allergic disorders:

hemophilia, Christmas disease, ITP, hemophilia, Christmas disease, ITP, angioneurotic edemaangioneurotic edema



DANAZOLDANAZOL

Major adverse effects:Major adverse effects: weight gain, edema, weight gain, edema, breast size, acne & breast size, acne &

oily skin, oily skin, hair growth, headache, hair growth, headache, deepening of voice, hot flushes, muscle deepening of voice, hot flushes, muscle crampscramps

Caution: hepatocellular damageCaution: hepatocellular damage

C/I: pregnancy & lactation C/I: pregnancy & lactation urogenital urogenital abnormalitiesabnormalities



MullerianInhibitoryfactor

both gametogenic & endocrine functions

Anterior Pituitary

Gonads: Gonads: TestisTestis

Sertoli cells

ESTRADIOL

Activin Inhibin TESTOSTERONE

(+)(-) (-)FSH

SEMINIFEROUS TUBULES

LH

LEYDIG CELLS

TESTOSTERONETESTOSTERONE most important androgen secreted by most important androgen secreted by

the testesthe testes 8 mg/day produced daily8 mg/day produced daily 95% by Leydig cells; 5% by androgens95% by Leydig cells; 5% by androgens Plasma levels: Plasma levels:

0.6 ug/dL after puberty0.6 ug/dL after puberty(declines after 50 years of age)(declines after 50 years of age)0.03 ug/dL = females0.03 ug/dL = females

TestosterTestosteroneone


HYPOTHALAMUS

GnRH Anterior Pituitary

LH

Testes

TESTOSTERONE

Dihydrotestosterone

Androgen Receptor Complex

Androgen Response Element

Expression of Appropriate genes in androgen-responsive cells

5α - Reductase

Ketoconazole

Spirinolactone

FINASTERIDE

Flutamide

Cyproterone

Spirinolactone

Other androgens/hormones produced:Other androgens/hormones produced:

dihydrotestosteronedihydrotestosterone androstenedioneandrostenedione dehydroepiandrosteronedehydroepiandrosterone pregnenolonepregnenolone progesterone & 17-hydroxylated progesterone & 17-hydroxylated

derivativesderivatives


BINDING:BINDING: 65% - SHBG65% - SHBG

2% - free2% - free

33% - albumin33% - albumin

METABOLISM:METABOLISM:

Testosterone converted to Testosterone converted to dihydrotestosteronedihydrotestosterone (major active (major active androgen) by 5-androgen) by 5--reductase-reductase


PHYSIOLOGIC EFFECTS:PHYSIOLOGIC EFFECTS:

A. Changes during pubertyA. Changes during puberty (Adrenarche)(Adrenarche) testosterone & 5testosterone & 5 dihydrotestosterone dihydrotestosterone

penile & scrotal growthpenile & scrotal growth skin skin pubic, axillary & beard hair pubic, axillary & beard hair

(Androstenedione, (Androstenedione, DHEA)DHEA)

more active sebaceous glands more active sebaceous glands thicker thicker & oilier skin& oilier skin larynx larynx vocal cords thicker vocal cords thicker low pitch voice low pitch voice skeletal growthskeletal growth


PHYSIOLOGIC EFFECTS:PHYSIOLOGIC EFFECTS:B. increase lean body massB. increase lean body mass

C. male development (2C. male development (2OO sexual characteristics) sexual characteristics) stimulate development & maturation of spermstimulate development & maturation of sperm stimulate development of the epididymis, vas stimulate development of the epididymis, vas

deferens, seminal vesicles, scrotum, penis, deferens, seminal vesicles, scrotum, penis, prostateprostate

D. anabolic effect on muscle & bone massD. anabolic effect on muscle & bone mass increase protein synthesis, decrease protein increase protein synthesis, decrease protein

breakdownbreakdown measured by measured by urine nitrogen secretion urine nitrogen secretion


PHYSIOLOGIC CHANGESPHYSIOLOGIC CHANGES

E. musculinization in females E. musculinization in females

F. metabolic effects:F. metabolic effects: hormone binding hormone binding liver synthesis of clotting factors, liver synthesis of clotting factors,

triglyceride, lipase, triglyceride, lipase, anti-trypsin anti-trypsin HDLHDL stimulate renal erythropoietin secretionstimulate renal erythropoietin secretion



PREPARATIONS:

Natural androgen: testosterone

Synthetic:Parenteral: ~ testosterone proprionate

~ testosterone enanthate~ testosterone cypionate

Oral: ~ Danazol~ Fluoxymesterone~ Methyltestosterone

Anabolic steroids: ~ Oxandrolone~ Stanozolol


1. Androgen replacement therapy in men1. Androgen replacement therapy in men hypogonadismhypogonadism pituitary deficiencypituitary deficiency given at puberty given at puberty growth spurt & 2 growth spurt & 2OO

sexual characteristicssexual characteristics Dosage: Dosage: Testosterone enanthrateTestosterone enanthrate

o 50 mg IM 50 mg IM qq 4 wks; then q 3 wks; then q 2 wks 4 wks; then q 3 wks; then q 2 wks (@ change at 3 mos interval)(@ change at 3 mos interval)

o double dosage at 100 mg q 2 wks until double dosage at 100 mg q 2 wks until maturation is complete maturation is complete then adult dose of then adult dose of 200 mg q 2 wks 200 mg q 2 wks

CLINICAL USES:CLINICAL USES:

Other drugs:Other drugs:Testosterone proprionateTestosterone proprionate

– – short DOAshort DOATestosterone undecanoateTestosterone undecanoate

– – asstd. with liver tumors asstd. with liver tumors

- 40mg/d p.o.- 40mg/d p.o.

Caution: reduce dose if (+) Caution: reduce dose if (+) polycythemia & HTNpolycythemia & HTN


2. Gynecologic disorders2. Gynecologic disorders reduce breast engorgement postpartumreduce breast engorgement postpartum DANAZOLDANAZOL = weak androgen for endometriosis = weak androgen for endometriosis Postmenopausal women: eliminate menstrual Postmenopausal women: eliminate menstrual

bleeding & enhance libidobleeding & enhance libido Premenopausal: chemotp of breast tumorsPremenopausal: chemotp of breast tumors

3. As Protein Anabolic agents3. As Protein Anabolic agents reverse protein loss after trauma, surgery, reverse protein loss after trauma, surgery,

prolonged immobilization, debilitating diseasesprolonged immobilization, debilitating diseases

TestosterTestosteroneoneCLINICAL USES:CLINICAL USES:


4. Anemia4. Anemia stimulates erythropoiesisstimulates erythropoiesis Aplastic anemia, Fanconi’s anemia, Sickle Aplastic anemia, Fanconi’s anemia, Sickle

cell anemia, Myelofibrosis, Hemolytic cell anemia, Myelofibrosis, Hemolytic anemiaanemia

5. Osteoporosis 5. Osteoporosis

6. Used as Growth Stimulator6. Used as Growth Stimulator stimulate boys with delayed puberty to stimulate boys with delayed puberty to

achieve expected adult heightachieve expected adult height too rapid or vigorous tp too rapid or vigorous tp accelerated accelerated

epiphyseal closureepiphyseal closure


7. Anabolic steroid & androgen abuse 7. Anabolic steroid & androgen abuse in sportsin sports

strength & aggressiveness strength & aggressiveness improved improved competetive performancecompetetive performance

8. Aging8. Aging androgen replacement: androgen replacement: lean body mass lean body mass

hematocrithematocrit

bone turnoverbone turnover

9. Carcinoma of the breast9. Carcinoma of the breast palliative effectpalliative effect act as antiestrogenact as antiestrogen


1. masculinizing effects in women: 1. masculinizing effects in women: hirsutism, clitorial enlargement, hirsutism, clitorial enlargement,

acne, deepening of voiceacne, deepening of voiceendometrial bleeding upon endometrial bleeding upon

discontinuationdiscontinuation

2. alteration in serum lipid profile:2. alteration in serum lipid profile: lower HDL2 and higher LDLlower HDL2 and higher LDL

3. sodium & water retention3. sodium & water retention

TestosterTestosteroneoneADVERSE EFFECTS:ADVERSE EFFECTS:

4. hepatic dysfunction:4. hepatic dysfunction: AST levels, AST levels, alkaline alkaline

phosphatase, phosphatase, bilirubin levels bilirubin levels hepatic adenomas; hepatocellular hepatic adenomas; hepatocellular

carcinomascarcinomas

5. Prostatic hyperplasia5. Prostatic hyperplasia

6. Behavioral changes 6. Behavioral changes physiologic dependence, physiologic dependence,

aggressiveness, psychotic aggressiveness, psychotic symptomssymptoms

TestosterTestosteroneoneADVERSE EFFECTS:ADVERSE EFFECTS:

1. pregnant women1. pregnant women

2. male patients with cancer of the 2. male patients with cancer of the breast & prostatebreast & prostate

3. infants & young children 3. infants & young children CNS effects CNS effects

4. renal & cardiac disease 4. renal & cardiac disease predisposd predisposd to edemato edema

5. patients with aplastic anemia treated 5. patients with aplastic anemia treated with androgen anabolic tp with androgen anabolic tp hepatocellular carcinomashepatocellular carcinomas

TestosterTestosteroneoneCONTRAINDICATIONSCONTRAINDICATIONS

::

Inhibition of Androgen Synthesis:Inhibition of Androgen Synthesis:

1. GnRH analogs1. GnRH analogs produce gonadal suppression when blood levels are produce gonadal suppression when blood levels are

continuous & not pulsatilecontinuous & not pulsatile

C.I.: prostatic carcinomaC.I.: prostatic carcinoma

Cause a significant surge of androgen secretion at the Cause a significant surge of androgen secretion at the beginning of therapy assted with a flare of tumor beginning of therapy assted with a flare of tumor activity & increase in symptomsactivity & increase in symptoms

Drugs:Drugs:1. LEUPROLIDE ACETATE1. LEUPROLIDE ACETATE - 1 mg SQ o.d.- 1 mg SQ o.d.2. GOSERELIN2. GOSERELIN

- once every 4 wks as SQ slow-release inj.- once every 4 wks as SQ slow-release inj.3. BUSERELIN3. BUSERELIN4. NAFARELIN4. NAFARELIN5. GONADORELIN5. GONADORELIN

Gonadal Gonadal InhibitorsInhibitorsAndrogen Androgen

SuppressionSuppression

A. Steroid Synthesis InhibitorsA. Steroid Synthesis Inhibitors

KETOCONAZOLEKETOCONAZOLE antifungal agent of imidazole classantifungal agent of imidazole class MOA: block cytochrome P450 enzymes involved in MOA: block cytochrome P450 enzymes involved in

gonadal & adrenal steroid hormone biosynthesisgonadal & adrenal steroid hormone biosynthesis Displaces estradiol & dihydrotestosterone from SHBGDisplaces estradiol & dihydrotestosterone from SHBG Tx of prostatic CATx of prostatic CA Revesible gynecomastia in malesRevesible gynecomastia in males

SPIRINOLACTONESPIRINOLACTONE A competetive inhibitor of aldosterone A competetive inhibitor of aldosterone MOA: weak inhibitor of the binding of androgen to MOA: weak inhibitor of the binding of androgen to

androgen receptorsandrogen receptors inhibits androgen biosynthesisinhibits androgen biosynthesis Cl. Use: women with hirsutismCl. Use: women with hirsutism S/E: metorrhagia – give with oral contraceptivesS/E: metorrhagia – give with oral contraceptives


Anti-AndrogenAnti-Androgen

B. 5B. 5 Reductase Inhibitors: Reductase Inhibitors:

FINASTERIDEFINASTERIDE a steroid-like inhibitor of 5a steroid-like inhibitor of 5 reductase reductase

conversion of testosterone to conversion of testosterone to dihydrotestosteronedihydrotestosterone

dihydrotestosterone in plasma & prostate dihydrotestosterone in plasma & prostate within 8O up to 24Owithin 8O up to 24O

CL. Uses:CL. Uses: benign prostatic hyperplasia: 5 mg/daybenign prostatic hyperplasia: 5 mg/day hirsutism in femaleshirsutism in females male pattern baldness: 1 mg/daymale pattern baldness: 1 mg/day


Anti - Anti - AndrogenAndrogen

Androgen Recptors Antagonists:Androgen Recptors Antagonists:1. CYPROTERONE ACETATE1. CYPROTERONE ACETATE

inhibits action of androgen at target inhibits action of androgen at target organorgan competes with dihydrotestosterone competes with dihydrotestosterone for binding to androgen receptor for binding to androgen receptor

acetate form acetate form with marked progestational with marked progestational effect effect suppress feedback enhancement suppress feedback enhancement of LH & FSHof LH & FSH

Clinical Uses:Clinical Uses: Hirsutism in females – 2 mg/d with estrogenHirsutism in females – 2 mg/d with estrogen Excessive sexual drive in men – 100 mg/dExcessive sexual drive in men – 100 mg/d Acne, male pattern baldness, virilizing Acne, male pattern baldness, virilizing

syndromessyndromes Precocious pubertyPrecocious puberty Prostatic hyperplasia & CAProstatic hyperplasia & CA


Anti - Anti - AndrogenAndrogen

Androgen Recptors Antagonists:Androgen Recptors Antagonists:

2. FLUTAMIDE2. FLUTAMIDE a nonsteroidal antiandrogen that acts like a a nonsteroidal antiandrogen that acts like a

competetive antagonist at androgen competetive antagonist at androgen receptorsreceptors

Cl.Uses:Cl.Uses: Prostatic CaProstatic Ca

Hirsutism in femalesHirsutism in females

causes mild gynecomastiacauses mild gynecomastia

mild reversible hepatic toxicitymild reversible hepatic toxicity



Androgen Recptors Antagonists:Androgen Recptors Antagonists:3.BICALUTAMIDE and NILUTAMIDE3.BICALUTAMIDE and NILUTAMIDE

potent orally active antiandrogenspotent orally active antiandrogens Cl.Use: metastatic prostatic carcinomaCl.Use: metastatic prostatic carcinoma

BicalutamideBicalutamide combined with GnRH analog to reduce combined with GnRH analog to reduce

tumor flaretumor flare dosage: single drug- 150-200 mg/d to dosage: single drug- 150-200 mg/d to

reduce reduce prostate-prostate-specific antigenspecific antigen

with GnRH analog– 50 mg/dwith GnRH analog– 50 mg/d NilutamideNilutamide

post-surgical castrationpost-surgical castration 300 mg/d for 30 days; ffd. by 150 mg/d300 mg/d for 30 days; ffd. by 150 mg/d



Androgen Receptors Antagonists:Androgen Receptors Antagonists:

4. SPIRINOLACTONE4. SPIRINOLACTONE An aldosterone antagonistAn aldosterone antagonist

Competes also with dihydrotestosterone for Competes also with dihydrotestosterone for androgen receptors in target tissuesandrogen receptors in target tissues

Reduces 17Reduces 17-hydroxylase activity -hydroxylase activity plasma plasma levels of testosterone & androstenedionelevels of testosterone & androstenedione

Cl.Use: hirsutism in women – 50-200 mg/dCl.Use: hirsutism in women – 50-200 mg/d


Anti -AndrogenAnti -Androgen

GOSSYPOLGOSSYPOL cottonseed derivativecottonseed derivative destroys elements of seminiferous tubules but destroys elements of seminiferous tubules but

donot alter endocrine function of the testisdonot alter endocrine function of the testis Dosage: Dosage:

20 mg/d X 2 mos, ffd. by maintenace dose of 60 mg/wk 20 mg/d X 2 mos, ffd. by maintenace dose of 60 mg/wk

(99% dev. Sperm count <4 million/ml)(99% dev. Sperm count <4 million/ml) Recovery ffg d/c: better if sperm ct donot fall to Recovery ffg d/c: better if sperm ct donot fall to

extremely low levels extremely low levels or or not more than 2 yrs. tp. not more than 2 yrs. tp. Major Adverse Effect: HYPOKALEMIA Major Adverse Effect: HYPOKALEMIA transient transient

paralysisparalysis Preparation: Oral tabsPreparation: Oral tabs

Intravaginal spermicide Intravaginal spermicide contraceptivecontraceptive

Gonadal InhibitorsGonadal InhibitorsChemical Contraception Chemical Contraception

in Menin Men

OTHER CHEMICAL CONTRACEPTIVES:OTHER CHEMICAL CONTRACEPTIVES:

1. 1. Testosterone Testosterone & & Testosterone enanthrateTestosterone enanthrate 400 mg/month (azoospermia in <50% of men)400 mg/month (azoospermia in <50% of men) minor adv. Rxn: gynecmastia, acneminor adv. Rxn: gynecmastia, acne

2. 2. Testosterone Testosterone + + DanazolDanazol not very effective not very effective

3. 3. TestosteroneTestosterone 100mg IM weekly + 100mg IM weekly + Levonorgestrel Levonorgestrel

500 mg p.o. (azoospermia in 94%)500 mg p.o. (azoospermia in 94%)

4. 4. Cyproterone acetateCyproterone acetate oligospermia oligospermia

5. 5. Testosterone + GnRHTestosterone + GnRH reversible reversible azoospermiaazoospermia

Gonadal InhibitorsGonadal InhibitorsChemical Contraception Chemical Contraception

in Menin Men

Mechanism of Action:Mechanism of Action:

selective inhibition of pituitary selective inhibition of pituitary function function inhibition of ovulationinhibition of ovulation

produce changes in the cervical produce changes in the cervical mucus, uterine endometrium, mucus, uterine endometrium, motility & secretion in the fallopian motility & secretion in the fallopian tubestubes

Hormonal Hormonal ContraceptionContraception

Pharmacologic Effects:Pharmacologic Effects: OvaryOvary

chronic use depresses ovarian functionchronic use depresses ovarian function on discontinuation: 75% ovulate in the 1st post tx cycleon discontinuation: 75% ovulate in the 1st post tx cycle

2% amenorrheic for several 2% amenorrheic for several yearsyears

UterusUterus cervix – hypertrophy & polyp formation; thicker & less cervix – hypertrophy & polyp formation; thicker & less

copious cervical mucuscopious cervical mucus ““19-nor” progestins 19-nor” progestins glandular atrophy & less glandular atrophy & less

bleedingbleeding

BreastBreast Estrogen containing agents Estrogen containing agents breast enlargement breast enlargement Es + Progestins Es + Progestins suppress lactation suppress lactation



Pharmacologic Effects:Pharmacologic Effects: CNSCNS

Es Es excitability excitability Prog Prog excitability; (+) thermogenic action excitability; (+) thermogenic action Profound changes in mood, affect & behavior Profound changes in mood, affect & behavior

used in tp of PMS, postpartum depression, used in tp of PMS, postpartum depression, climacteric depressionclimacteric depression

EndocrineEndocrine alter adrenal structure & functionalter adrenal structure & function attenuation of ACTH reponse to metyraponeattenuation of ACTH reponse to metyrapone alterations in angiotensin-aldosterone system alterations in angiotensin-aldosterone system

( ( plasma renin activity; plasma renin activity; aldosterone secretion) aldosterone secretion) TBG TBG total plasma thyroxine (T4) total plasma thyroxine (T4) plasma SHBGplasma SHBG

Pharmacologic Effects:Pharmacologic Effects: BloodBlood

serious thromboembolic phenomena serious thromboembolic phenomena in serum iron & total iron binding capacityin serum iron & total iron binding capacity

LiverLiver reduce flow of bile reduce flow of bile cholelithiasis cholelithiasis

LipidsLipids Es Es serum triglycerides & cholesterol serum triglycerides & cholesterol

phospholipidsphospholipids HDL & HDL & LDL LDL Es + Prog Es + Prog slight slight in triglycerides & HDL in triglycerides & HDL


Pharmacologic Effects:Pharmacologic Effects:

Carbohydrate metabolismCarbohydrate metabolism rate of absorption from the GITrate of absorption from the GIT Prog - Prog - basal insulin level; produce progressive basal insulin level; produce progressive

on glucose tolerance which is reversible on on glucose tolerance which is reversible on discontinuationdiscontinuation

CVSCVS small small in CO, higher SBP, DBP and HR in CO, higher SBP, DBP and HR

SkinSkin pigmentation (chloasma)pigmentation (chloasma) sebum production sebum production acne acne



Oral contraception Oral contraception

– – pregnancy rate = 0.5 to 1/100 pregnancy rate = 0.5 to 1/100 woman years at riskwoman years at risk

EndometriosisEndometriosis


PREPARATION:PREPARATION:

I. Combination Oral ContraceptivesI. Combination Oral Contraceptives

1. 1. MonophasicMonophasic – constant amount of – constant amount of estrogen and progesterone estrogen and progesterone throughout 21 day cyclethroughout 21 day cycle

2. 2. Biphasic Biphasic – constant amount of estrogen – constant amount of estrogen with varying amounts of progestinswith varying amounts of progestins

3. 3. TriphasicTriphasic – varying amounts of – varying amounts of estrogen & progestinsestrogen & progestins


Adverse Effects:Adverse Effects:

MildMild::Nausea, myalgia, breakthrough bleeding, edemaNausea, myalgia, breakthrough bleeding, edemaChanges in serum proteins & other endocrine Changes in serum proteins & other endocrine

fxnsfxnsHeadacheHeadacheNo withdrawal bleedingNo withdrawal bleeding

ModerateModerate: : requires discontinuationrequires discontinuationBreakthrough bleeding – bi- & tri-phasic causes Breakthrough bleeding – bi- & tri-phasic causes

bleeding bleedingWeight gainWeight gain skin pigmentationskin pigmentationAcne, hirsutismAcne, hirsutismUreteral dilation, vaginal infectionsUreteral dilation, vaginal infectionsAmenorrhea Amenorrhea


ADVERSE EFFECTS:ADVERSE EFFECTS: SevereSevere::

Vascular disorders – Venous thromboembolic Vascular disorders – Venous thromboembolic diseasedisease

- M.I., Cerebrovascular disease- M.I., Cerebrovascular diseaseGIT disorders - GIT disorders - cholestatic jaundicecholestatic jaundice

symptomatic GB diseasesymptomatic GB diseasehepatic adenomashepatic adenomasischemic bowel diseaseischemic bowel disease

DepressionDepression

CancerCancer

OthersOthers: alopecia, erythema multiforme, erythema : alopecia, erythema multiforme, erythema nodosumnodosum


DRUG INTERACTIONS: DRUG INTERACTIONS:

Phenytoin - Phenytoin - catabolism of catabolism of contraceptivescontraceptives

Antibiotics – those that interfere with Antibiotics – those that interfere with normal GI flora who normal GI flora who enterohepatic enterohepatic cycling & bioavailability of estrogencycling & bioavailability of estrogen

Potent hepatic inducers (Rifampin) - Potent hepatic inducers (Rifampin) - liver catabolism of Es & Progliver catabolism of Es & Prog


CONTRAINDICATIONS & CAUTIONS:CONTRAINDICATIONS & CAUTIONS:

Thrombophlebitis / thromboembolic Thrombophlebitis / thromboembolic phenomenonphenomenon

CV disordersCV disorders Vaginal bleeding if cause is unknownVaginal bleeding if cause is unknown Known or suspected tumor of the breast or Known or suspected tumor of the breast or

other estrogen-dependent neoplasmother estrogen-dependent neoplasm CHF or other edemaCHF or other edema Fibroid tumors – use progestational agents Fibroid tumors – use progestational agents

alonealone Adolescents whose epipjhyseal closure is not Adolescents whose epipjhyseal closure is not

yet completedyet completed


PREPARATION:PREPARATION:

Progesterone Oral Contraceptives:Progesterone Oral Contraceptives:I. Oral formulation (Norethindrone, Norgestrel)I. Oral formulation (Norethindrone, Norgestrel)

““mini-pill”mini-pill” less effectiveless effective

II. Subdermal (Norgestrel)II. Subdermal (Norgestrel) delivered via 6 silastic tubes implanted in delivered via 6 silastic tubes implanted in

the upper armthe upper arm lasts 5-6 yearslasts 5-6 years disadv:disadv: need for surgical incisionneed for surgical incision irregular bleedingirregular bleeding IC HTN – rareIC HTN – rare


CLINICAL USES:CLINICAL USES: pts. with hepatic diseases, HTN, prior TE, pts. with hepatic diseases, HTN, prior TE,

psychosis, mental retardationpsychosis, mental retardation

SIDE EFFECTS:SIDE EFFECTS:Headache, dizziness, bloating & weight Headache, dizziness, bloating & weight

gain gain reversible reduction of glucose tolerancereversible reduction of glucose tolerance


Estrogen aloneEstrogen alone Combination Estrogen + Progestins Combination Estrogen + Progestins → →

“MORNING AFTER”“MORNING AFTER” Schedules:Schedules:

Conjugated Estrogen:Conjugated Estrogen: 10 mg TID X 5 days10 mg TID X 5 days Ethinyl Estradiol:Ethinyl Estradiol: 2.5 mg BID X 5 days2.5 mg BID X 5 days Diethylstilbesterol:Diethylstilbesterol: 50 mg OD X 5 days50 mg OD X 5 days L-Norgestrel:L-Norgestrel: 0.75 mg BID X 1 day0.75 mg BID X 1 day Norgestrel 0.5 mg with ethinyl estradiol 0.05 mg.Norgestrel 0.5 mg with ethinyl estradiol 0.05 mg.

4 mg immediately then 2 tabs at 12 hours 4 mg immediately then 2 tabs at 12 hours S/E: N & V, HA, dizziness, breast tenderness, S/E: N & V, HA, dizziness, breast tenderness,

abdominal & leg crampsabdominal & leg cramps MIFEPRISTONEMIFEPRISTONE

• Antagonistic at progesterone & glucocorticoid Antagonistic at progesterone & glucocorticoid receptorsreceptors

• (+) luteolytic effect(+) luteolytic effect• Combined with prostaglandinsCombined with prostaglandins

Post Coital Post Coital ContraceptionContraception

““Men do not usually Men do not usually give themselves any give themselves any

reasons for marrying…reasons for marrying…

… … except except that they that they want to want to

marry that marry that particular particular woman”woman”

gonadal drugs ma. janetth b. serrano, m.d., dpba

Documents

ovary slide

pituitary slide

dpba slide

ovary quiescent

ovary disturbances

pituitary prolactinomas

receptor shbgbound estrogens

estrogen response elements