Ovarian hormones • Estrogen• Progesterone• Small amounts of androgens
– Testesterone(<200mcg \d)– Androstenedione
• Converted to testosterone and estrone in peripheral
– Function:1. Normal hair growth2. Female libido3. Metabolic effects
• inhibin – Inhibit FSH secretion
• Activin – Increase FSH secretion
• Relaxin – Decrease uterine contraction– Increase glycogen synthesis
Org
an sy
stem
effe
cts
f est
roge
n
Estrogen
Maturation and secndary sex
characters in females
Endocrine :1- decrease FSH &LH
2-increase the renin activity
Sebum Acne
Hair growth
Pigmentation
TG,HDLLDL
CNS:1.Excitation
2.Sense of well being
Other Estrogen effects
Increase endometrial
growth
Decrease osteocalstic
activity
Increase synthesis of
clotting factors
x,ix,vii,iiAnd increase synthesis of
antithrombin
Induce synthesis of
progesterone receptors
Affect behavior and
libido in humans
Stimulate central
component of stress system:
1-increase production of
CRH2-Increase activity of symathetic
Facilitate loss of
intravascular fluid to the
extracellular
Also estrogen elevate the levels of :thyroxine,iron copper why?
Clinical uses of estrogen
• Primary hypogonadism • Postmenopausal hormonal therapy• Contraception • Hairsutism
Uterine bleeding Increase risk of
endometrial cancer
May increase risk of breast cancer
N&V,breast tenderness,
increase the of :1-frequency of
migraine2- Cholestasis
3- hypertension
Side effects
Abnormal uterine bleeding
Thromboembolic disorders
Cholestasis and liver diseases
High risk of estrogen dependent canrcinoma
Psychosis
Smokers
Cont
rain
dica
tions
Org
an sy
stem
effe
cts
of p
roge
ster
one
Progesterone
Endocrine :1- decrease FSH &LH
2-increase the renin activity
Sebum Acne
Hair growth
CNS:1.Depression
2.Thermogenic effect 3-hypnosis
• Increase the synthesis of aldosterone• Sodium water retention Compete with
aldosterone on its receptor
• Stimulate lipoprotein lipase• Increase basal insulin levels • Increase glycogen storage• Promotes ketogenesis
Metabolic effects
1. Also progesterone is responsible for alveolobular production in the breast 2. Maturation and secretory changes of the endometrium 3. Increase the ventilatory response to PCO2
Clinical uses
• Contraception • Hormonal replacement therapy • Premenstrual syndrome • Diagnostic test:– Test the estrogen secretion • Progesterone 150mg\d or medroxyprogesterone 10mg\
day is given for 5-7 days ,this regimen will be followed by bleeding in amenorrheic pts only when the endometrium is stimulated by estrogens
Drugs that affect gonadal hormones
Hormonal antagonist
Progesterone antagonist
Progesterone with
antiandrogenic activity
Selective estrogen receptor
modulators
Estrogen antagonist
Sex hormones synthesis inhibitors
GnRH continuous
administration
GnRH antagonists
Aromatase inhibior
5-alpha reductase
others
Ovulation inducing agents Hormonal analogues
Oral contraceptives
Hormonal replacement
therapy
hormonal contraception
Female contraception
Before conception
Combined pills
Monophasic
Biphasic
Triphasic Progesterone only pillsAfter
conception
Male contraception
Testosterone alone
Testosterone +progesterone
Female contraceptionbefore conception
• Pills or implants or IM injection are taken to prevent conception
• Combined or mini pills
1-Combined pills
• Contain estrogen or its derivatives and progesterone or its derivatives
• According to progesterone concentration in the pills we divide the combined pills to 3 subtypes:1. Monophasic 2. Biphasic 3. Triphasic
•Constant Estrogen &Progesterone levels throughout the cycle
Monophasic •Dose
of one(progesterone) or both (E+P) is changed once during the cycle
Biphasic
•Dose of one(progesterone) or both (E+P) is changed twice during the cycle
Triphasic
The main advantage of bi and tri phasic administration
• Decrease the progesterone administration• Thus decrease the SE’s
Progesterones
Highly androgenic
Norgestrel
Levo-norgestrel
Moderate-Low androgenic Norethindrone
Very low androgenic
Desogestrel
Nogestimate
Anti androgenic Cyproterone
Progesterone mechanism of action as contraceptive
• Inhibit ovulation 70-80%– Alteration in gonadotropin pulsing– Decrease pituitary gland response to GnRH
• Alter cervical mucosa • Increase endometrial secretion • Decrease peristalsis
The zygote unable to implant
Side effects and C\I of progesterones
• Increase the risk of osteoporosis• Increase risk of atherosclerosis • wt gain • Decrease in glucose tolerance
How to administer the combined pills?
• Take it daily for 21 days then 7 days free why?– To resemble the normal menstrual cycle
Benefits
• Decrease ovarian cancer• Decrease the endometrial cancer – Estrogen only products increase the risk of
endometrial cancer why?
Side effects of long term use of OC’s
• DVT• PE• Studies fail to approve the increased risk of
breast cancer• Gall bladder disease
Do OC’s cause infertility ?
• Chronic use depresses ovarian function • Ovaries become smaller• Majority of pts return to normal menstrual
patterns when the drug is discontinued • 75% will ovulate in the first posttreatment cycle• 97% will ovulate by the 3rd posttreatment cycle • About 2% remain amenorrheic for periods up
to several yrs
2- Minipills
• Contain only progesterone or its derivatives • Norgestrel and norethindrone are the most
widely used progesterone • Minipills must be used continuously without
free intervals like combined pills• Used in women when:– Estrogen is not desiered or C\I• Lactating women bec. Estrogen suppress the lactation
– Lactating women seeking contraception
Emergency Contraception
• Plan B / Morning After Pill– 0.75 mg levonorgestrel X 2 - within 5 days of unprotected
sex• Mechanism:– Inhibit LH surge – Thickens cervical mucus– Possible interference with fertilization or implantation
• WILL NOT HARM AN ESTABLISHED PREGNANCY!!!
• Now OTC!!!
Medical Abortion
• Mifepristone / RU-486– Inhibits progesterone receptors causing disruption at
implantation siteor
• Methotrexate– Inhibits dihydrofolate reductase (stops rapidly dividing
cells)
• Used with misoprostil– Prostaglandin analog produces uterine contractions
• Cheap, common medication also used for: arthritis, ulcers, constipation, cervical ripening
Preparation available
• Oral tablet• Implants – Norgestrel implant
• Intramuscular injection – Medroxyprogesterone
• Vaginal rings • Hormonal Intrauterine devices
Day after contraception
• Taken after unprotective sexual intercoarse• Exact mechanism of action unknown may be:
1. Inhibit ovulation 2. Inhibit transport of fertilized egg
• Efficacy 75-80%when taken within 72 hr after fertilization
• 3 approaches :1. High dose of estrogen and progesterone 2. Estrogen only • Must be combined with antiemetic drug
3. Mifeproston +misoprostol
Mifeproston
• Progesterone receptor antagonist– Also it is aglucocorticoid antagonist
• Used as an abortifacient in the first two months of pregnancy
• In smaller doses as an emergency contraceptive– Given along with misoprostol once within 72 hr
from unprotective coitus
Male contraception
• The identical agent is1. Decrease the spermatogenesis• Difficult to reach bec. Inhibition of 99% of sperms
would result in enough sperms for fertilization
2. No erectile dysfunction3. No decrease in libido
Mechanism of action of both testosterone and progesterone in male contraception
Decrease gonadotropins Decrease FSH
&LHDecrease
spermatogenesis
Hormonal antagonist
• We have talked about progesterone agonist and cyproterone
• Now ,we will talk about Selective estrogen receptor modulators SERM
SERMs uses
Tamoxifen,toremifene
• Breast cancer treatment • Prevent breast cancer in
high risk pts • Adjuvant in pts after
lumpectomy • May improve manic
episodes in pts with bipolar disorder(2007 study)
• Angiogenesis in cancer(see next slide)
• Gynecomastia• Anovulatory cycle in
inferile women • Retroperitoneal fibrosis
Ralixofen
• Osteoprosis treatment and prevention
• May have preventive effect on breast cancer
Clomiphene
• Induce ovulation
SERMs special considerations• Increase the risk of endometrial cancer• Not to be used more than 5 yr• Hot flushes N&V are common side effects• Taken 10-20 mg twice daily
Tamoxifen
• Has no thing to do with pituitary failure• Taken 100mg\day for 5 days usually at 3rd—5th day of the
menstrual cycle • SE: hot flushes, N&V, ovarian enlargement ,heavy
menses,headache,wt gain, multiple pregnancy(10%),may increase risk of ovarian cancerClomiphene