Sei sulla pagina 1di 29

Female Sex Hormones ,

Oral contraceptives
and Fertility agents

ARLENE MACEREN – DIAZ, M.D, FPSECP


PHARMACOLOGY DEPT
MATIAS H. AZNAR MEMORIAL
COLLEGE OF MEDICINE
SOUTHWESTERN UNIVERSITY
 ESTROGENS
TWO CHEMICAL CATEGORIES
3. THOSE WITH A STEROID NUCLEUS
4. THOSE WITHOUT ( NON-STEROIDAL
CPDS WITH ESTROGENIC ACTIVITY)

I.=STEROIDAL , NATURAL
A. ESTRADIOL ( ESTRADIOL 17B, E2)
B. ESTRONE (E1)
C. ESTRIOL (E3)
 ESTRADIOL- IS THE MAJOR ESTROGEN
SYNTHESIZED AND SECRETED BY THE
NORMAL OVARY

 ESTRONE – IS PRODUCED BY THE OVARY


AND LIVER (MOSTLY FROM
ESTRIOL)FROM ESTRADIOL OR IN
PERIPHERAL TISSUES FROM
ANDROSTENEDIONE AND OTHER
ANDROGENS

 ESTRIOL -IS THE ESTROGEN THAT IS


SYNTHESIZED BY THE FETO-PLACENTAL
UNIT
A. II- STEROIDAL , SYNTHETIC
B. ETHINYL ESTRADIOL
C. MESTRANOL
D. QUINESTROL

III- NONSTEROIDAL, SYNTHETIC


ESTROGENS
G. DIETHYLSTILBESTROL
H. CHLOROTRIANISENE
I. METHALLENESTRIL
PHARMACOKINETICS
 ESTROGENS ARE HIGHLY PROTEIN BOUND, THEY
ARE TRANSPORTED IN THE BLOOD BOUND TO SERUM
ALBUMIN AND SEX HORMONE BINDING GLOBULIN

 ONLY THE UNBOUND FREE ESTROGENS ARE


BIOLOGICALY ACTIVE

 LARGE AMOUNTS OF ESTROGEN IN THE FREE FORM


ARE EXCRETED BY THE LIVER IN THE BILE AND
UNDERGOES ENTEROHEPATIC RECYCLING
 NATURALLY OCCURING STEROID ESTROGEN ARE
SUBJECT TO A LARGE FIRST PASS METABOLISM IF
ADM. ORALLY IT PRODUCE LOW BIOAVAILABITY
 ESTERIFIED OR CONJUGATED
DERIVATIVES OF NATURAL ESTROGEN
AS WELL AS SYNTHETIC ESTROGENS
ANALOGS ARE WELL ABSORBED
AFTER ORAL ADM. AND ADM. TO THE
SKINAND MUCOUS MEMBRANES.

 SYNTHETIC ESTROGENS (e.g. ETHINYL


ESTRADIOL)= UNDERGOES LESS FIRST
PASS METABOLISM
 PREMARIN –ORAL PREPARATION OF
CONJUGATED ESTROGENS ( CONTAINS
SULFATE ESTERS OF ESTRONE AND
EQUILIN) OBTAINED FROM PREGNANT
MARE’S URINE
 DIETHYLSTILBESTROL – A
NONSTEROIDAL CPD. THAT IS ORALLY
ACTIVE AND HAS A RELATIVELY LONG
DURATION OF ACTION
 MESTRANOL (SYNTHETIC)- IS QUICKLY
OXIDIZED TO ETHINYL ESTRADIOL
WHICH IS METABOLIZED MORE SLOWLY
THAN THE NATURALLY OCCURING
ESTROGENS BY THE LIVER AND
PERIPHERAL TISSUES. BEING FAT
SOLUBLE THEY ARE STORED IN THE
ADIPOSE TISSUES FROM WHICH THEY
ARE SLOWLY RELEASED. THEY HAVE
PROLONGED ACTION AND HIGHER
POTENCY THAN THE NATURAL
ESTROGENS
 METABOLISM OF ESTROGENS
ESTROGENS ARE HYDROXYLATED
IN THE LIVER , THEN GLUCURONIDATED OR
SULFATED.THE INACTIVE PRODUCTS ARE
EXCRETED IN THE URINE.

MECHANISM OF ACTION OF ESTROGENS


STEROID HORMONES BINDS TO SPECIFIC
ESTROGEN RECEPTORS . THE RECEPTOR
IS A MEMBER OF SUPERFAMILY OF
RECEPTORS THAT INCLUDE RECEPTOR
FOR THYROID HORMONE AND VITAMIN D
 ACTIVATED STEROID RECEPTOR
COMPLEX INTERACTS WITH THE
NUCLEAR CHROMATIN TO INITIATE
HORMONE SPECIFIC RNA
SYNTHESIS,RESULTING IN THE SYNTHESIS
OF SPECIFIC PROTEINS THAT MEDIATE A
NUMBER OF PHYSIOLOGIC FUNCTIONS
 THERAPEUTIC USES OF ESTROGEN
A. IN POSTMENOPAUSAL WOMEN AS
HORMONE REPLACEMENT THERAPY

DOSE - WOMEN W/ UTERUS – 0.3-1.25 mgs


a day of Conjugated estrogen (PRIMARIN) or
0.01-0.02mgs/day of ethinyl estradiol on the first
day of a 21-25 days menstrual cycle then add
10 mgs of medroxyprogesterone during the
last 10-14 days.
Women whose uterus was surgically remove can be
given unopposed estrogen therapy

1. Contraindications of hormonal replacement


2. Family history of breast cancer
3. Deep vein thrombosis
4. Severe liver dysfunction
5. Pulmonary embolism
6. Cerebro-vascular accident
7. Myocardial infarction
1. BENEFITS ASSOCIATED WITH
POSTMENOPAUSAL ESTROGEN REPLACEMENT
( HRT )
2. DECREASE POSTMENOPAUSAL DISTURBANCE
OF SLEEP.
3. CARDIOVASCULAR EFFECT- ESTROGEN
PROVIDES A PROTECTIVE EFFECT AGAINST
CARDIOVASCULAR DISEASE CAUSING A
DECREASE IN LDL AND AN INCREASE OF HDL.
4. UROGENITAL TRACT-REVERSES
POSTMENOPAUSAL ATROPHY OF VULVA,
VAGINA,URETHRA AND TRIGONE OF THE
BLADDER
5. OSTEOPOROSIS- ESTROGEN DECREASES THE
RESORPTION OF BONE BUT HAS NO EFFECT
ON BONE FORMATION
ESTROGEN DECREASES FREQUENCY OF HIP
FRACTURE ( ADD CALCIUM 1,000 TO 1,500 mgs /day
+ EXERCISE )
IN ORDER TO PREVENT OSTEOPOROSIS
TREATMENT WITH ESTROGEN MUST BEGIN
WITHIN 2-3 yrs OF MENOPAUSE
5. VASOMOTOR SYMPTOMS –ESTROGEN RE-
ESTABLISHES FEEDBACK ON HYPOTHALAMIC
CONTROL OF NOREPINEPHRINE SECRETION
LEADING TO DECREASE FREQUENCY OF “HOT
FLASHES”

• RISK OF REPLACEMENT THERAPY- BREAST CA,


ENDOMETRIAL CA ; GALLBLADDER DISEASE
CON’T OF USES OF ESTROGEN

B. PRIMARY HYPOGONADISM- AS REPLACEMENT


THERAPY IN ESTROGEN –DEFICIT PATIENT DUE
TO PRIMARY FAILURE OF DEVELOPMENT OF
OVARIES OR DUE TO CASTRATION
TREATMENT SHOULD BEGIN AT 11- 13 yrs OLD TO
STIMULATE DEVELOPMENT OF SECONDARY
SEX CHAR., MENSES AND OPTIMAL GROWTH

ADVERSE EFFECTS OF ESTROGEN


7. NAUSEA AND VOMITING
8. MIGRAINE HEADACHE
9. HYPERPIGMENTATION
4. CHOLESTASIS 7. POSTMENOPAUSAL
5. HYPERTENSION BLEEDING
6. ADENO CA OF THE VAGINA ( IN YOUNG WOMEN
WHOSE MOTHER HAS BEEN TREATED WITH
DIETHYLSTILBESTROL EARLY IN PREGNANCY )

ANTIESTROGENS- ARE DRUGS W/C


MODIFY THE ACTION OF ESTROGEN
1. CLOMIPHENE ( CLOMID )- CLOSELY RELATED TO
ESTROGEN CHLOROTRIANISENE
 ACTIVE ORALLY

MECH. OF ACTION –IT IS A WEAK ESTROGEN OR A


PARTIAL AGONIST/ANTAGONIST-W/C INTERFERS
WITH THE NEGATIVE FEEDBACK OF ESTROGEN ON
THE HYPOTHALAMUS AND PITUITARY RESULTING
TO INCREASE SECRETION OF GONADOTROPIN-
RELEASING HORMONE ( Gn-RH ) AND
GONADOTROPINS LEADING TO A STIMULATION
OF OVULATION
USES : TO TREAT INFERTILITY ASSOC WITH
ANOVULATION CYCLES ( NOT IN PITUITARY OR
OVARIAN FAILURE )
DOSE : 100mgs / day FOR 5 DAYS STARTING ON THE 5TH
DAY OF MENSES

ADVERSE EFFECTS:
6. HOT FLUSHES
7. OVARIAN ENLARGEMENT
8. MULTIPLE PREGNANCY -10%
1. TAMOXIFEN- MECH. OF ACTION – COMPETES
FOR BINDING OF ESTROGEN TO THE RECEPTOR

USES: PALLIATIVE TREATMENT OF ADVANCED


BREAST CA IN POSTMENOPAUSAL WOMEN

ADVERSE EFFECT :
6. HOT FLUSHES
7. NAUSEA AND VOMITING
8. MENSTRUAL IRREGULARITIES
THE PROGESTINS

PROGESTERONE- MOST IMPORTANT


PROGESTIN PRODUCED BY THE CORPUS
LUTEUM OF THE OVARY, TESTIS AND
ADRENAL GLDS FROM CIRCULATING
CHOLESTEROL IN PREGNANCY-
PLACENTA.

PHARMACOKINETICS: RAPIDLY ABSORBED


FOLLOWING ANY ROUTE OF ADM. HALF
LIFE =5 min. . IT IS STORED IN BODY FAT
IN THE LIVER IT IS METABOLIZED TO
PREGNANEDIOL AND CONJUGATED WITH
GLUCORONIC ACID AND EXCRETED INTO THE
URINE AS PREGNANEDIOL GLUCURONIDE.

URINARY PREGNANEDIOL = THE INDEX OF


PROGESTERONE SECRETION.

PROGESTATIONAL AGENTS
ARE SYNTHETIC CHEMICALS CLOSELY RELATED
TO PROGESTERONE
2 TYPES
A. 21CARBON COMPOUND- WHICH CAN PRODUCE
A SECRETORY ENDOMETRIUM AND MAINTAIN
PREGNANCY
C-21 PROGESTERONE
 PROGESTERONE
 6 METHYL-17α ACETOXYPROGESTERONE
(MEDROXYPROGESTERONE)
 17α –ACETOPROGESTERONE
 6 α- METHYL-6 DEHYDRO-17α
ACETOXYPROGESTERONE

B. PROGESTINS DERIVED FROM C19-


NORTESTOSTERONE
 19- NORTESTERONE
 17α ETHINYL-19-NORTESTOSTERONE
( NORETHISTERONE , NORTHINDRONE)
3. NORETHYNODREL
4. LYNESTRENOL
5. NORETHINDRONE ACETATE
6. NORGESTROL
7. ETHYNODIOL DIACETATE

CLINICAL USES
8. PROGESTIN CHALLENGE TEST –TO TEST FOR
THE DIFFERENTIAL DIAGNOSES OF
AMENORRHEA.
9. DYSFUNCTIONAL UTERINE BLEEDING
3. CONTINOUS PROGESTIN THERAPY TO TREAT
a) ENDOMETRIOSIS
b) ENDOMETRIAL CA- MEGESTROL ACETATE
4. LUTEAL PHASE DEFECT ASSOC. WITH HABITUAL
ABORTION
5. CONTRACEPTION- MEDROXYPROGESTERONE
ACETATE AND NORETHINDRONE ENANTHATE

ADVERSE EFFECTS:
8. EDEMA AND DEPRESSION
9. ANDROGEN LIKE PROGESTINS ( NORGESTREL
AND NORETHINDRONE CAN INCREASE RATIO OF
LDL TO HDL –
10. AND MAY CAUSE THROMBOPHLEBITIS,
11. PULMONARY EMBOLISM
12. ACNE ,HIRSUTISM AND WT. GAIN
ANTIPROGESTIN
MIFEPRISTONE ( RU486 )- IS A POTENT
ANTIGLUCOCORTICOID THAT HAS A PARTIAL
PROGESTERONE ANTAGONIST- AGONIST
ACTIVITY. IT IS AN ABORTIFACIENT AGENT.

ORAL CONTRACEPTIVES

3 CLASSIFICATION
7. FIXED COMBINATION –CONTAIN CONSTANT
AMOUNTS OF ESTROGEN (ETHINYL ESTRADIOL
AND A PROGESTIN ( NORETHINDRONE )
2. MULTIPHASIC COMBINATION – CONTAIN
CONSTANT AMOUNTS OF ESTROGEN BUT
VARIABLE DOSE OF PROGESTIN

3. MINIPILLS- CONSIST ONLY OF PROGESTIN AT A


CONSTANT DOSE

MECHANISM OF ACTION :
6. INHIBIT MID-CYCLE LHsurge, THUS INHIBITING
OVULATION
7. THICKENS CERVICAL MUCUS
8. ALTERS SECRETORY CHANGES OF
ENDOMETRIUM
9. ALTERS TUBAL TRANSPORT
OTHER KINDS OF HORMONAL
CONTRACEPTION
1. PROGESTIN IMPLANTS- LEVONOGESTREL

2. POSTCOITAL COTRACEPTION –HIGH DOSES OF


ETHINYL ESTRADIOL OR DIETHYLSTILBESTROL
WITHIN 72 hrs OF COITUS FOR 5 DAYS

3. MORNING AFTER PILL – 2 DOSES OF ETHINYL


ESTRADIOL + NORGESTREL ARE GIVEN 72 HRS OF
COITUS FOLLOWED BY ANOTHER 2 DOSES 12HRS
LATER
ADVERSE EFFECTS
2. BREAST FULLNESS
3. DEPRESSION
4. DIZZINESS, NAUSEA AND VOMITING
5. THROMBOEMBOLISM, THROMBOPHLEBITIS,
6. HYPERTENSION, MI, CVA
7. CHOLESTATIC JAUNDICE

CONTAINDICATIONS
10. CVA
11. ESTROGEN DEPENDENT CA
12. LIVER DISEASE
13. MIGRAINE
SELECTIVE ESTROGEN RECEPTOR MODULATOR
( SERM )-
RALOXIFENE (EVISTA) = HAS SELECTIVE AGONIST
OR ANTAGONIST ACTIVITIES ON TISSUES
RESPONSIVE TO ESTROGEN. IT ACTS AS AN
AGONIST ON BONE AND PARTIALLY ON
CHOLESTEROL METABOLISM
(DECREASE TOTAL AND LDL CHOLESTEROL)
IT IS AN ANTAGONIST ON HYPOTHALAMUS OR IN
UTERINE AND BREAST TISSUES
ASSOC. WITH INCREASE RISK OF VENOUS
THROMBOEMBOLIC EVENT
USES: REPLACEMENT THERAPY IN CLIMATERIC
FOR PREVENTION OF OSTEOPOROSIS , TO
DECREASE SYMPTOMS OF MENOPAUSE
 DRUGS AND DIETARY SUPPLEMENTS USED
IN THE TREATMENT OF OSTEOPOROSIS
1. ALENDRONATE
-DECREASES BONE TURNOVER,
-INHIBITS OSTEOCLAST ACTIVITY
2. CALCITONIN SPRAY
-INTERFERES WITH OSTEOCLASTS AND INHIBITS
BONE RESORPTION
3. CALCIUM CARBONATE SUPPLEMENTS-
1,200mgs /day
4. ESTROGENS ( COMBINED WITH A PROGESTIN )
5. SERM- RALOXIFEN

Potrebbero piacerti anche