Gonadal Hormones and Inhibitors

The GONADAL
HORMONES and
INHIBITORS
Drugs for Reproductive Endocrinology
Leonila A. Estole-Casanova, MD
Department of Pharmacology and Toxicology
University of the Philippines – College of Medicine
September 9, 2008
The Gonadal Hormones and Inhibitors : Drugs for Reproductive

Outline
I. Review of the Menstrual Cycle &
Steroidogenesis
II. Female Gonadal Hormones
Estrogen and Progesterone
ORAL CONTRACEPTION
V. Estrogen and Progesterone Inhibitors and
antagonists
VI. Male Gonadal Hormones
VII. Antiandrogens

Outline
q Review of the Menstrual Cycle &
Steroidogenesis
q Female Gonadal Hormones
Estrogen and Progesterone –
ORAL CONTRACEPTION
antagonists
VII. Antiandrogens

Hypothalamic Pituitary Ovarian
Axis
+/- hypothalamus
↓ + GnRh
+/- Pituitary
↓ + LH and FSH
ovary
progesterone
estrogen
Follicular growth and ovulation

Gonadal Hormones
 Steroid hormones are derived from
cholesterol
 Normal human ovary produces all three
classes of SEX STEROIDS divided
into main groups according to the number
of carbon atoms they possess:
3. 21 carbon series – PROGESTINS (pregnane
nucleus)
4. 19 carbon series - ANDROGENS
(androstane nucleus)
5. 18 carbon series - ESTROGENS (estrane
nucleus)
Outline
q Review of the Menstrual Cycle and
Steroidogenesis
q Female Gonadal Hormones
ORAL CONTRACEPTION
antagonists
VII. Antiandrogens

The Estrogens
 Major natural estrogens in human:
O
CH3
CH3 OH
CH3 OH
H
H H OH
H H
H H H H
HO
HO HO
ESTRONE
ESTRADIOL ESTRIOL
 Actions mediated by ESTROGEN RECEPTORS

(alpha and beta) which are ligand-regulated
transcription factors
Some synthetic estrogens

The Estrogens: Physiologic
Effects
 Required for sexual maturation of the
female
 Promote endometrial proliferation during
follicular phase
 Block resorption of bone
 Increase the levels of HDL and triglycerides
and decrease the levels of LDL and total
cholesterol
 Increase SHBG, TBG, CBG, renin substrate
 Increase the levels of Factors II, VII, IX, X
The Induce
Gonadal the synthesis of progesterone

Hormones and Inhibitors : Drugs for Reproductive
The Estrogens:
Pharmacokinetics
 Estradiol (E2) binds STRONGLY to α globulin
(SHBG)
LOWER affinity to albumin
 E2 (liver) → Estrone (E1) and Estriol (E3)

→ hydroxylated derivatives and
conjugated metabolites
 Orally administered estrogens have HIGH ratio

of hepatic to peripheral effects
→ responsible for the increased
clotting factors and increased
The renin substrate
Gonadal Hormones and Inhibitors : Drugs for Reproductive
The Progestins
 Progesterone is the most
important progestin in human
 Actions mediated by
progesterone receptors (A and B
isoforms) which are ligand-
activated transcription factors
 Decreases amount of cervical
mucus and increases its
viscosity
 Promote endometrial
development during luteal phase
 Increases basal body
temperature

The Progestins
 Stimulate growth and dev’t of breasts

during pregnancy
 Its effects on the uterus are essential for
maintainance of pregnancy
 Antagonize actions of aldosterone

The Progestins:
Pharmacokinetics
 Progesterone is rapidly absorbed following
administration by any route
 t ½ is 5minutes
 Almost completely metabolized in one
passage through the liver

Outline
Steroidogenesis
Oral contraception
antagonists
VII. Antiandrogens

Hormonal contraception in
women
 Combination of progestins and

estrogens – Combination oral
contraceptives (COCs)
 Progestin only pills (POPs)

Combination Oral
Contraceptives (COCs)
19
Combination Oral
Contraceptives (COCs) –
ESTROGEN component
20
The Pharmacology of the
Estrogen Component of COCs
 E2 is the most potent natural estrogen ---
inactive orally
 E2 + ethinyl group at the 17 position =
Ethinyl Estradiol
--- orally active

Estrogen Component of COCs
 Metabolism of EE VARIES
SIGNIFICANTLY from individual to
individual, and from one population to
another
 ESTROGEN CONTENT of the pill is of major

clinical importance ---- THROMBOSIS is
dose-related
 DOSE OF ESTROGEN – a critical issue in

selecting an oral contraceptive
Combination Oral
Contraceptives (COCs) –
PROGESTIN component
23
Progestin Component of COCs
 2 major types of synthetic progestins
q Derivatives of 19 nortestosterone
q Derivatives of 17α acetoxyprogesterone

TESTOSTERONE ETHISTERONE NORETHINDRONE
 Removal of 19-carbon from ethisterone

formed NORETHINDRONE → changed
major hormonal effect from an
androgen to progestational agent
→ 19 nortestosterone - all
progestational agents have some degree
of androgenic activity
19 NORTESTOSTERONE
ESTRANES GONANES
 Norethindrone  Levonorgestrel
 Norethynodrel  Norgestimate*
 Norethindrone  Gestodene*
acetate  Desogestrel*
 Ethynodiol
acetate * With greater
progestational
activity
 Norethindrone family
(most are converted to the parent
compound, norethindrone)
 Norethindrone
 Norethynodrel
 Norethindrone acetate
 Ethynodiol diacetate
 Lynestrenol
 Norgestrel

 Other progestins
 Levonorgestrel is the active isomer of
norgestrel
 New progestins
 Desogestrel, gestodene, norgestimate are
derivatives of levonorgestrel
 Reduced androgenicity (increased sex
hormone binding globulin, decreased free
testosterone)
 Drospirenone – analogue of spironolactone,
has affinity for mineralcorticoid receptor
and antimineralcorticoid effect (Yasmin)
17 α ACETOXYPROGESTERONE
 C21 progestins
 PREGNANES
 Structurally related to progesterone
 Medroxyprogesterone acetate and
megestrol acetate
 Marketed for noncontraceptive usage
 Injectable depomedroxyprogesterone
acetate
COCs
“ Current formulations of
COCs are made from
SYNTHETIC steroids and
contain no natural
estrogens or progestins.”

COCs
synthetic
Ethinyl estradiol
progestins

Definitions
Low Dose Oral Contraceptives – products with
<50ug of EE
1st generation COCs – products with > 50ug of
EE
2nd generation COCs – products with
levonorgestrel,
norgestimate, and other members of
the norethindrone family and
<50ug EE
3rd generation COCs – products with
desogestrel or
The gestodene and <50ug
Gonadal Hormones of EE : Drugs for Reproductive
and Inhibitors
Types of COCs
 Usually containing ethinyl estradiol and
norethindrone
 Administered with interruption (21 days on,
7 days off)
 Monophasic: All 21 active pills contain
same amount of Estrogen/Progestin (E/P)
 Biphasic: 21 active pills contain 2
different E/P combinations (e.g., 10/11)
 Triphasic: 21 active pills contain 3
different
The E/P combinations
Gonadal Hormones (e.g.,
and Inhibitors : Drugs6/5/10)
for Reproductive
COCs Mechanism of Action
Progestin suppresses LH Suppress ovulation
Estrogen suppresses FSH
secretion
secretion
Reduce sperm P
transport in upper r
genital tract
(fallopian tubes) o
Change endometrium g
making implantation e
less likely s
Thicken cervical
mucus (preventing t
sperm penetration) i
n

Oral Contraceptive Pills

COCs: Efficacy
 Perfect use failure rate: 0.1%
 Typical use failure rate: 7.6%
 Pregnancies usually occur because initiation
of the next cycle is delayed
 Strict adherence to 7-pill free days is critical
to obtain contraception
 If with vomiting & diarrhea → back-up
method for 7days
→ put pill in the vagina

COCs: Metabolic Effects

COCs: Metabolic Effects -
Thrombosis
Thrombosis can be divided into 2 major
categories:
2. Venous thromboembolism
deep vein thrombosis
pulmonary embolism
5. Arterial thrombosis
myocardial infarction
stroke

Thrombosis
 Pharmacologic estrogen increases the
production of clottign factors (II, VII, IX, X)
 Progestins have no significant impact on

clotting factors
 Past users of oral contraceptives DO NOT have

an increases incidence of cardiovascular
disease
 Hypertension is a very important additive risk

The factor forHormones
Gonadal stroke inand
OC Inhibitors
users : Drugs for Reproductive
Thrombosis
 All low dose OCs, regardless of progestin type,
have an increased risk of VTE, concentrated in
the 1st 2 years of use
 Recent studies reinforce the belief that the
risks of arterial and venous thrombosis are a
consequence of the ESTROGEN component of
COCs
 Smoking has a lesser effect on the risk of
venous thrombosis compared with arterial
thrombosis
 Smoking and estrogen have an additive effect
on the risk of arterial thrombosis
Thrombosis
 Low dose OCs DO NOT increase the risk of MI
or stroke in healthy, non-smoking women,
regardless of age
 Almost all MI and strokes in OC users occur in

users of HIGH dose products or users
WITH CARDIOVASCULAR RISK FACTORS
 Cardiac deaths occurred in only in women who

smoked >15 cigarettes
per day

Thrombosis
 New studies emphasize the importance of good
patient screening
- arterial thrombosis is limited to older
women who smoke or have cardiovascular
risk factors
- no increase in mortality due to MI or stroke
in healthy, non-smoking women
 If a patient has a family history of idiopathic

thromboembolism, an evaluation to search for
an underlying abnormality in the coagulation
system is warranted
Conclusion
“ LOW DOSE oral contraceptives

are VERY SAFE
for
healthy young women.”

COCs : Carbohydrate
Metabolism
 Older high dose OCs – (+) impaired glucose
tolerance
 Insulin sensitivity is affected mainly by the

PROGESTIN component of the pill
 Glucose intolerance is dose-related
 Insulin and glucose changes with low dose

monophasic and multiphasic OCs are so
minimal and clinically insignificant
COCs : Carbohydrate
Metabolism
“ It can be stated definitely that

oral
contraceptive use
DOES NOT produce
an increase in
diabetes mellitus.”

COCs: The Risk of Breast
Cancer
 Current and recent (1-4years) use of OCs
may be associated with 20% increased
risk of early (<35) premenopausal breast
cancer, essentially limited to localized and a
vey small increase in the number of actual
cases
 May be due to:

1.) detection/surveillance bias
2.) accelerated growth of already present
malignancies
COCs: The Risk of Breast
Cancer
 NO EFFECT of past use or duration of OC use
(up to 15 years of continuous use)
 NO INCREASED RISK on use of high dose OCs
 Previous use may be associated with a
REDUCED RISK of metastatic cancer LATER
in life, and REDUCED RISK of
postmenopausal breast cancer
 NO INCREASED RISK in women with positive
family history for breast cancer/women with
benign breast disease

COCs: Contraceptive Benefits
 Most important use is for ORAL
CONTRACEPTION
 Pelvic examination not required to initiate
use
 Do not interfere with intercourse
 Few side effects
 Convenient and easy to use
 Client can stop use
 Can be provided by trained non-medical
staff
48
COCs: Noncontraceptive
Benefits
1. Incidental benefits
2. Benefits to treat and manage problem and
disorders
49
COCs: Incidental Benefits
 LESS ENDOMETRIAL CANCER
Use for 12 months reduces the risk by
50%
Greatest protective effect if use for >3
years
 LESS OVARIAN CANCER

Risk is reduced by 40% (3 years) to 80%
(>10 years of use)

COCs: Incidental Benefits
 Fewer ectopic pregnancies
 More regular menses – less flow,
dysmenorrhea, anemia
 Less salpingitis
 Increased bone density
 Possibly less benign breast disease
 Possibly fewer ovarian cysts

COCs: Noncontraceptive
Benefits
q Incidental benefits
q Benefits to treat and manage problem
and disorders
Dysmennorhea
Endometriosis
Replacement therapy in ovarian
dysfunction
DUB
Postmenopausal symptoms
52
COCs: Absolute
Contraindications
1. Thrombophlebitis, thromboembolic
disorders, cerebrovascular disease,
coronary occlusion or past history of these
conditions
2. Severe hypercholesterolemia or
hypertriglyceridemia
3. Untreated hypertension
4. Smokers over the age of 35
5. Known or suspected breast cancer
6. Markedly impaired liver function
7. Undiagnosed abnormal vaginal bleeding
COCs: Relative
Contraindications
1. Systemic lupus erythematosus
2. Sickle cell disease
3. Gestational diabetes mellitus
4. Diabetes mellitus
5. Hyperlipidemia
6. Controlled hypertension
7. Smoking
8. Migraine headaches
9. Seizure disorder

COCs: Relative
Contraindications
1. Hepatic disease
2. Obstructive jaundice in pregnancy
3. Gallbladder disease
4. Mitral valve prolapse
5. Uterine leiomyomas
6. Elective surgery

Clinical Decisions: Surveillance
 Can be prescribed without a clinical breast
and pelvic examination
 Patients need be seen only every 12months
 Perform yearly breast and pelvic
examination on follow up
 Reassess new users within 1-2months
 “ COCs are safer than most people
think. ”
 FEAR OF SIDE EFFECTS: most
common reason why patients
Thediscontinue oral and
Gonadal Hormones contraception
Inhibitors : Drugs for Reproductive
Clinical Decisions: Surveillance
 Laboratory surveillance should be used
only when indicated
 The ff patients should be monitored with
blood screening tests for glucose, lipids
and lipoproteins:
Young women, at least once
Women >35 y/o
Women with strong family history of heart
disease, DM,HPN
Women with GDM
Obese women
COCs: Choice of Pill
 The therapeutic principle remains:
“ Utilize the formulations

that give
effective contraception and
the greatest margin of safety.”

 Current data support that there is
GREATER safety with low dose
preparations
 There is LITTLE difference between the
COCs: Pill taking
 Effective contraception is present during
the first cycle of pill use, provided the pills
are started not later than the fifth day of
the cycle and no pills are missed
 Starting COCs on Day 1 o f menses ensure
immediate protection
 Some suggest starting on first Sunday
following onset of menses
 Usually avoids menstrual period on weekends
 Most clinicians recommend backup for 7
days
COCs: Initiating Method
 “Quick start”
 Starting the day of the counseling visit
regardless of patient’s day in her cycle
 Ensure not pregnant before starting
 Use backup method for 7 days
 Patients will not experience an increase
in BTB (breakthrough bleeding)

COCs: Pill taking
 Monthly, periodic or no bleeding is an
individual patient’s choice
 • No rationale for recommending a pill-
free interval to “rest”
 Serious side effects are not eliminated by
pill-free intervals (e.g. risk DVT)
 If pill free intervals are used, important to
not exceed 7 pill-free days
 However, studies have shown patients
who lengthened pill-free interval up to 11
days failed to show signs of ovulation

COCs: Pill taking
How important is it to take
OC at the same time
every day?
 Precise pill taking minimizes
breakthrough bleeding
 Compliance is improved by a
fixed schedule that is habit
forming

COCs: Clinical Problems
 Breakthrough bleeding
 Amenorrhea
 Weight gain
 Acne
 Ovarian cysts
63
COCs: Clinical problems
BREAKTHROUGH BLEEDING
2. Irregular bleeding in the first few months
after starting oral contraception
3. Unexpected bleeding after many months of
use
* There is NO evidence that the onset of

bleeding is associated with decreased
efficacy; no matter what oral contraceptive
formulation is used, even the
lowest dose products
 Most frequently encountered occurs in the
first few months of use
 Higher in women who smoke
 Best managed by ENCOURAGEMENT &
REASSURANCE
 Disappears by the 3rd cycle
 Represents tissue breakdown as the
endometrium adjusts from its usual thick
state to the relatively thin state allowed by
hormones in OC
 BB after many months of use is a
consequence of progestin-induced
decidualization
 Endometrium and blood vessels within the
endometrium tend to be fragile and prone
to breakdwon and asynchronous bleeding

 2 factors associated with BB:
3. Inconsistency of pill taking- more important
and has a greater effect in later cycles
4. Smoking – exerts a general effect at any
time
 REINFORCEMENT OF CONSISTENT PILL-

TAKING can help minimize BB

 If bleeding occurs before the end of the
cycle –
stop the pills
wait 7 days
start a new cycle
 If BB is prolonged or is aggravating to the

7 days
patient --
Conjugated estrogen 1.25mg
Estradiol and
The Gonadal Hormones 2mgInhibitors : Drugs for Reproductive
 Taking of 2-3 pills is NOT effective
 The PROGESTIN component will always
dominate – doubling the pills → double the
progestational impact → double the
decidualizing and atrophic effect on the
endometrium and destabilizing effect on
endometrial blood vessels
 ADD ESTROGEN ( do not add progestin)

AMENORRHEA
 With low dose pills, the estrogen content is
not sufficient to stimulate endometrial
growth
 Progestational effect dominates to such a
degree that a shallow atrophic
endometrium is produced, lacking sufficient
tissue to yield withdrawal bleeding →
AMENORRHEA
 There is no harmful permanent
consequence of amenorrhea while on OC
 ANXIETY in both patient and clinician --
AMENORRHEA
 Patient is anxious because of uncertainty
regarding pregnancy
 Clinician is anxious because of medicolegal
concerns stemming from old studies which
indicated increased risk of congenital
abnormalities
 Recent reviews showed that there is NO
ASSOCIATION between oral contraception
and increased risk for congenital
malformation and there is NO increased risk
The of having
Gonadal abnormal
Hormones and children
Inhibitors : Drugs for Reproductive
AMENORRHEA
 Incidence <2% in the 1st year of use
 Incidence INCREASES with duration of use
(5%)
 Management problem → ADEQUATE
COUNSELLING

WEIGHT GAIN
 Frequently cited as a major problem with
compliance
 Studies FAIL to demonstrate a significant
weight gain with OC
 Major problem of perception – supported by
the finding that weight gain was identical in
treated and placebo groups
 Clinician has to REINFORCE the LACK OF
ASSOCIATION between low dose OCs &
weight gain and FOCUS on the real culprit:
diet and level of exercise
COCs : Ovarian Cysts
 Functional ovarian cysts occurred less
frequently in women on higher dose oral
contraception
- this protection is reduced with current
lower dose products
 Ovarian cysts can be encountered in
patients taking any of the oral
contraceptive formulation

COCs: Drugs that Affect Efficacy
 No evidence that antibiotics can affect OC
efficacy
 Patients on the ff medications should

choose an alternative contraceptive:
Carbamazepine
Phenytoin
Phenobarbital
Rifampicin
Ethosuzimide
COCs: Drugs that Affect Efficacy
 OCs potentiate the action of
Diazepam
Chlordiazepoxide
Tricyclic antidepressants
Theophylline
 LOWER doses of the above agents in OC
users
 OCs alter clearance rates of Paracetamol

and ASA
 LARGER
The doses may
Gonadal Hormones and be required
Inhibitors in for
: Drugs OC users
Reproductive
Progestin-Only Pills (POPs)
77
POPs: Mechanisms of Action
Suppress ovulation
(not consistently suppressed)
? Reduce sperm transport

in upper genital tract
(fallopian tubes)
Change endometrium
making implantation
less likely
Thicken cervical mucus
(preventing sperm
penetration)

POPs: Mechanisms of Action
 Contains a small dose of a progestational
agent
 Must be taken daily in a continuous fashion
 Must be taken every day of the SAME TIME
 Change in cervical mucus
- requires 2-4hours to take effect
- impermeability diminishes 22 hours after
administration
- by 24hours sperm penetration is essentially
unimpaired
POPs: Efficacy
 Effective when taken at the same time every
day (0.05–5 pregnancies per 100 women during
the first year of use)

POPs: Contraceptive Benefits
 Pelvic examination not required prior to use
 Do not interfere with intercourse
 Do not affect breastfeeding
 Immediate return of fertility when stopped
 Few side effects
 Convenient and easy-to-use
 Client can stop use
 Can be provided by trained nonmedical staff
 Contain no estrogen
81
POPs: Noncontraceptive
Benefits
 May decrease menstrual cramps

 May decrease menstrual bleeding
 May improve anemia
 Protect against endometrial cancer
 Decrease benign breast disease
 Decrease ectopic pregnancy
 Protect against some causes of PID
82
POPs: Problems
 Irregular menstrual bleeding – major reason
why women discontinue POPs
 More functional ovarian cysts
 Levonorgestrel associated with acne

POPs: Pill taking
 Minipill should be started on the first day of
menses
 Back-up method must be used for the 1st
seven days because some women may
ovulate as early as 7-9 days after menses
 Pill intake should be keyed to a daily event
to ensure regular administration at the
same time of the day
 Missed pills – take missed pill ASAP, back-
up method should be used until resumed
for at least 2 days
The
 IfGonadal Hormones and Inhibitors : Drugs for Reproductive
more than 3hrs late – back-up method for
POPs: Clinical Decisions
 2 situations in which excellent efficacy is
achieved:
2. Lactating women
- no evidence of any adverse effect on
breastfeeding
- women breasfeed longer and add
summplementray feeding at a later time
- can be started IMMEDIATELY after delivery
7. Women age over 40

Outline
Steroidogenesis
Estrogen and Progesterone - Oral
contraception
q Estrogen and Progesterone
Inhibitors and antagonists
q Male Gonadal Hormones
q Antiandrogens

SERMs
 Competitive partial agonist inhibitor of
estradiol at the estrogen receptor
 Clomiphene
 Tamoxifen
 Raloxifene

Selective estrogen receptor
modulators (SERMs) and estrogen
receptor antagonists
Bone Breast CV Uterus
system
estradiol Ag Ag Ag Ag
Clomiphene Antag Antag Antag Antag
ICI 182 780
tamoxifen Ag Antag Ag Ag
raloxifen Ag Antag Ag Antag

Ovulation Induction:
 Stimulate ovulation in women with
oligomenorrhea or anovulation
 Blocks the feedback inhibitory influence of
estrogens on the hypothalamus → surge of
gonadotropins → ovulation

Ovulation Induction
 Clomiphene at the start of the menstrual
cycle to prevent inhibitory effect of
estrogen on FSH secretion
 Clomiphene followed by FSH to stimulate
follicular growth and hCG to stimulate
ovulation
 Long acting GnRH agonists (or
antagonists) to inhibit pituitary function
followed by FSH to stimulate follicular
growth and hCG to stimulate ovulation
Aromatase inhibitors
 Inhibits conversion of testosterone to

estradiol
 Useful in treatment of breast cancer
 Can be steroidal (formestane and
exemestane) or non steroidal
( anatrazole, letrozole)

Progesterone receptor
antagonists
 RU 486 (mifepristone)
 Used for abortion (together with a
prostaglandin agonist)
 Post coital contraception
 Also a glucocorticoid receptor antagonist
 ZK 98734 (lilopristone)
 Experimental stage
 Also a glucocorticoid receptor antagonist

Male Gonadal
hormones

Hypothalamic Pituitary Testicular
Axis
hypothalamus
↓ + GnRh
Pituitary
↓ + LH and FSH
testes
Androgens T DHT

Androgens and Anabolic
Steroids
 Testosterone – most important androgen
secreted by the testis
 95% produced by the Leydig cells; 5% by
the adrenal gland
 65% of circulating T is bound to SHBG
 2% remains free and available to enter cells
and bind to intracellular receptors
 T is converted to DHT by 5α reductase
 Conversion of T to E2 by P450 arom

Testosterone
 Ineffective when given orally but can be
administered transdermally or parenterally
 Testosterone esters can be given
intramuscularly
 17 α- alkylated androgens are effective
when given orally but has more side
effects, especially hepatic toxicity

Physiologic Effects: Androgens
 General growth promoting properties of
androgens on body tissues
 Responsible for penile and scrotal growth
and changes in the skin ( appearance of
pubic, axillary and beard hair)
 Stimulate skeletal growth and epiphyseal
closure
 Play an important role in stimulating and
maintaining sexual function in men
 Increase lean body mass
 Decrease SHBG, HDL; Increase LDL
Some synthetic androgens

Mechanism of Action:
Androgens
 T acts intracellularly
 T → DHT (skin, prostate, seminal vesicles,
epididymis)
 All actions are mediated by the androgen
receptor which is a ligand activated
transcription factor
 T and DHT bind to intracellular androgen
receptor → growth, differentiation,
synthesis of proteins

Androgen therapy
 Main use as replacement therapy in male
hypogonadism
 Treatment of catabolic states
 Adverse reactions
Virilization (in females, prepubertal boys)
Feminization (males)
Suppression of HPG axis
Edema, jaundice, hepatic carcinoma

Anti-androgens
 5α reductase inhibitors:
 Finasteride: treatment of BPH and male
pattern baldness
 Androgen receptor antagonists
Cyproterone acetate – for hirsutism
Flutamide, biclutamide, nilutamide:
treatment of prostate cancer, hirsutism,
CAH and male precocious puberty
Spironolactone – aldosterone antagonist ,
for hirsutism

Gonadal Hormones and Inhibitors

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Gonadal Hormones and Inhibitors

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The GONADAL

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 Actions mediated by ESTROGEN RECEPTORS

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 E2 (liver) → Estrone (E1) and Estriol (E3)

 Orally administered estrogens have HIGH ratio

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 Stimulate growth and dev’t of breasts

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 Combination of progestins and

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 ESTROGEN CONTENT of the pill is of major

 DOSE OF ESTROGEN – a critical issue in

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

TESTOSTERONE ETHISTERONE NORETHINDRONE

 Removal of 19-carbon from ethisterone

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 Progestins have no significant impact on

 Past users of oral contraceptives DO NOT have

 Hypertension is a very important additive risk

 Almost all MI and strokes in OC users occur in

 Cardiac deaths occurred in only in women who

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 If a patient has a family history of idiopathic

“ LOW DOSE oral contraceptives

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 Insulin sensitivity is affected mainly by the

 Glucose intolerance is dose-related

 Insulin and glucose changes with low dose

“ It can be stated definitely that

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 May be due to:

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 LESS OVARIAN CANCER

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

“ Utilize the formulations

the greatest margin of safety.”

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

* There is NO evidence that the onset of

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 REINFORCEMENT OF CONSISTENT PILL-

The Gonadal Hormones and Inhibitors : Drugs for Reproductive

 If BB is prolonged or is aggravating to the