REPRODUCTIVE DRUGS

ESTROGEN RECEPTOR MODULATORS

Not hormones/ replacement
Affect specific estrogen receptor sites
Develop to produce the positive effects of estrogen
DRUGS:
Raloxifene (Evista)
Toremifene (Fareston)
Given oral
C/I: venous thrombosis; smoking - risk for blood clots
A/R:
Headache; dizziness
visual changes
Hot flashes
Vaginal bleeding
Drugs Affecting the Reproductive System
Female hormones:
Estrogen and Progesterone
Example: Oral contraceptives (OCPs)
Estrogen prevents ovulation
Impt for development of female repro system & secondary characteristics.
Progesterone prevents implantation of ovum
decreases amount and increases viscosity of cervical mucous to impair sperm
motility
impedes motility of the ova by affecting peristalsis of the ovaduct.
ESTROGENS
PROGESTINS
Replacement therapy
Used as contraceptives; combined
with estrogens
Palliation of menopause discomfort
Treat primary and secondary
Treat female hypogonadism
amenorrhea
Prevent postpartum breast
engorgement
Treat functional uterine bleeding
Slow bone loss in osteoporosis
Treat specific cancers
Affect release of FSH and LH
Make endometrium secretory
Cause capillary dilation
Inhibit secretion of FSH and LH
Fluid retention
Prevent follicle m maturation and
ovulation
Thin cervical mucus

Inhibit uterine contractions

Conserve calcium and phosphorus
Cross placenta
Inhibit ovulation
Enter breast milk
Proliferate endometrial lining
Protect heart from atherosclerosis
Cross placenta


C/I:

A/R:

Enter breast milk

Idiopathic vaginal bleeding
Breast cancer
Estrogen-dependent cancers
Hx of thromboembolism
CVA
Smokers
Pregnancy;breastfeeding
Metabolic bone ds
Breakthrough bleeding
Menstrual irregularities
Dysmenorrhea
Amenorrhea
Changes in libido

C/I:

PID
STIs
Endometriosis
Migraine headaches
Asthma
Cardiac ds
Renal dysfunction

A/R:

Nervousness
Constipation
Breast enlargement
Perineal pain
Endometriosis
Abortion
PID
Expulsion of IUD
Irritation (vaginal use)

Progestogens
Used for hormonal contraception and for producing long-term ovarian suppression for
other purposes (e.g., dysmenorrhea, endometriosis, hirsutism and bleeding disorders)
when estrogens are contra-indicated
Estrogens
Estradiol (estrace)
Esterified estrogen (menest)
Conjugated estrogens (premarin)
Estropipate (orthoEst)
Progestins
Drospirenone (Yasmin)
Etonogestrel vaginal ring
Medroxyprogesterone (provera)
Stimulate female reproductive
Norgestrel (ovrette)
system
Levonorgestrel (mirena)

FERTILITY DRUGS - Stimulate female reproductive system

Cetrorelix (Cetrotide) - inj
Follitropin beta (follistim) - inj
Clomiphene (clomid) - oral
Menotropins (pergonal) - inj
Infertility Drugs
Example: Clomid

Stimulates secretion of FSH and LH, which stimulates maturation of follicles, ovulation
and development of the corpus luteum.
Uses: Inadequate ovulation, low sperm count in males.
Adverse Effects: Similar to those of OCPs. Increased incidence of early abortion and
multiple births, pelvic pain.

Clomifene and Tamoxifen anti-estrogens work by inhibiting the negative feedback

of estrogens in the hypothalamus Incr release of LH and FSH.
Gonadotropins used in women who lack approp pit function or do not respond to
clomifene therapy. Treatment starts with daily inj of menotrophin (LH = FSH amts) or
urofollitropin (FSH), followed by 1-2 large doses of chorionic gonadotropin (mostly LH) to
induce ovulation.
Adverse Effects? Multiple births
In men with hypogonadotrophichypogonadism, both LH and FSH are given to stim
spermatogenesis and androgen release.
Directly stimulate follicles and ovulation
Stimulate functioning ovaries
Stimulate the hypothalamus to increase FSH and LH
Given in sequence with HCG
Menotropins stimulate spermatogenesis in males
Check estrogen and estradiol levels
d/c drug ovarian overstimulation
C/I:
Primary ovarian failure
Pregnancy
Thyroid or adrenal dysfunction
IUB
Ovarian cysts
A/R:
Multiple births
Fluid retention
Birth defects
Uterine bleeding
Ovarian overstimulation abdl pain,
Ovarian enlargement
distention, ascites, pleural effusion
gynecomastia

Oxytoxics
Examples: Pitocin (oxytocin)
Enhances contractile activity of the uterine smooth muscle.
Adverse Effects: Uterine rupture, fetal hypoxia or trauma, hypertension, CVA.
Uses: Post-partum hemorrhage only.
Premature Labor Inhibitor
Examples: Yutopar (rotodrine)
Selective 2 adrenergic receptor antagonist that prevents smooth muscle contractions.
Uses: Preterm labor if gestation > 20 weeks.
Adverse Effects: palpitations, tachycardia, hypotension.
Oral Contraceptives
Uses: Contraception, menstrual irregularities.
Adverse Effects: hypertension, diabetes, high LDL, dizziness, numbness, weight gain,
fluid retention, breast tenderness, breakthrough bleeding.
Contraindications: ABSOLUTE: Thromboplebitis, CVA, breast cancer, pregnancy, liver
disease or impairment, CAD, > 35, smoker.
Combination Pills contain estrogen: ethinylestradiol and progestogen, taken for ~ 21
days and discontinued for the following 6-7 days to allow menstruation to occur.
Progestogen-only Pills contain low dose of progestogen, taken continuously.
Fertilization
Oral Contraceptives - Mechanism
Combination pills act by feedback inhibition on the hypothal to supressGnRH and hence
plasma gonadotropin secretion.
Produce an endometrium that is unreceptive to implantation.
Alter ovaduct motility.
Change the composition of cervical mucous.
These latter effects also caused by progestogen-only pills and appear to be the basis of
their contraceptive actions.
Block ovulation in only ~ 25% of women.
Menstruation often stops initially with progestogens, but usually returns with prolonged
use.
But the length and duration of bleeding highly variable.
Combination of both E and P most potent and effective way to suppress GnRH, LH,
and FSH secretion.
The combined effects on previous slide >99% efficacy.
Ethinylestradiol or mestranol the E in the combination contraceptives.
The progestins all are potent PR agonists, but also have some androgenic crossreactivity.
Norgestrel and levonorgestrel>norethindrone and norethindrone acetate >ethynodiol,
norgestimate, gestodene, anddegestrel in androgenic activity.
Oral Contraceptives
3 Delivery systems are available: vaginal ring, transdermal patches, oral tablets.
Ring contains ethinylestradiol and a progestin, etonogestrel.
Has zero-order pkinetics over 21 days.
Dermal patch has ethinylestradiol and a progestin, norelgestromin. Changed weekly for
3 weeks.

Oral Contraceptives Adverse Effects

Non-life Threatening
Breakthrough bleeding and irregular menses (most women who take combo pills).
Abdominal pain
Chest pain, cough, dyspnea, dizziness, numbness, headache, nausea, changes in libido,
breast soreness.
Eye problems: vision loss or blurred.
Severe leg pain (calves, thighs).
Hirsutism, vaginal yeast infections and depression.
~ 20-30 % women experience some of these effects.
Oral Contraceptives Adverse Effects Serious
Rare.
Cholestatic jaundice and thromboembolic disease.
Thromboembolism (~ 25/10,000 women).
Emergency (morning-after) Contraception levenorgestrel a single high dose can be
taken up to 3 days after unprotected intercourse. Blocks the LH surge.
Therapeutic Termination of Pregnancy mifepristone a progesterone ant highly
effective in terminating early pregnancy (up to 63 days gestation) when used with a PGcervical ripening agent (e.g., gemeprostpessaries). [Recall Progesterone supports
endometrial implantation of fertilized ovum].
-Main adverse effect: pain and bleeding.
Stimulate uterine contraction
Effective in gravid uterus
Stimulate lacteal glands
Prevent uterine atony after delivery
Cross placenta
Enter breast milk
Cross placenta
Enter breast milk
C/I:
CPD
Uterine atony
Early pregnancy
CAD; HPN - BP
A/R:
Uterine hypertonicity
Uterine spasms
Uterine rupture
Hemorrhage
Fetal distress
Male Hormones
Example: Testosterone
Secreted by the testes.
Uses: Treatment of low sperm count and impotence caused by any kind of deficiency.
Aromatase Inhibitors
Used to inhibit estrogen-dependent tumors, metastatic breast cancer.
But, serious estrogen-lacking side-effects: increased risk of osteoporosis.
Anastrozole, letrozole, exemestane, formestane.
Selective Estrogen Receptor Modulators (SERMs)

class of compounds that act on the estrogen receptor.

Are mixed agonists/antagonists.
ER and ER types are tissue-specific.
The actions of SERMs on various tissues:
Bone turnover and postmenopausal osteoporosis respond favorably to most SERMs,
although premenopausal women may experience bone loss with some SERMs including
tamoxifen.
Breast - all SERMs decrease breast cancer risk, and tamoxifen is mainly used for its
ability to inhibit growth in estrogen receptor-positive breast cancer.
Cholesterol and triglycerides - levels respond favorably to SERMs.
Deep venous thrombosis - the risk may be elevated in at least some SERMs.
Hot flashes are increased by some SERMs.
Pituitary gland - clomifene blocks estrogen action, leading to an increase of folliclestimulating hormone andluteinizing hormone.
Uterus - tamoxifen may increase endometrial carcinoma risk, but raloxifene and
femarelle do not. Data on toremifene and clomifene is insufficient.

Name

clomifene

femarelle

ormeloxifene

raloxifene

toremifene

Uses

Effects/location

used in anovulation

antagonist at hypothalamus

managing menopause
symptoms, osteoporo
sis

agonist at brain and bone

agonist at bone; antagonist at

breast and uterus
agonist at bone; antagonist at
breast and uterus

contraception

osteoporosis, breast
cancer

breast cancer

lasofoxifene

osteoporosis, breast
cancer,

vaginal
atrophy

tamoxifen

breast
cancer

agonist at the bone, antagonist

at breast and uterus

agonist at bone and uterus,

antagonist at breast

Undescended testicles.
Anabolic action in conditions such as osteoporosis, anemia, and debilitated states.
Inoperable breast cancer in postmenopausal women.
Adverse Effects: Edema, acne, hirsutism, voice deepening, polycythemia, increased
LDL, depression.
Contraindications: Pregnancy, prostate cancer, breast cancer in males.
Sex hormones; produced in the adrenal glands
Indicated for hypogonadism (underdevelop testes)
Treat certain breast cancers
Adrenal Sex Hormones

Androgens male hormones secreted by the adrenal cortex in both sexes and are
responsible for the physiological effects exerted by adrenal sex hormones.
The incr protein synthesis (anabolism), which incr muscle and bone mass and strength,
affect development of male 2 characteristics. They incr hair growth and libido in
women. Excessive secretion: masculine effects in women.
Female sex hormones exert few effects. Excessive secretion: feminine characteristics in
men.
Androgen Receptor Antagonists
Flutamide and spironolactone used to treat metastatic prostate cancer and BPH.
Progesterone Receptor Antagonists
Mifepristone (aka RU-486) used to induce 1st-trimester abortion.
Often admin with misoprostol (PG analogue) stimulates uterine contractions.
Asoprisnil does not cause abortion, but inhibits the growth of tissue derived from the
endometrium and myometrium.
May be used to treat endometriosis and uterine fibroids.
Estrogenic compounds span a spectrum of activity ranging from:
full agonists (agonistic in all tissues) such as the natural endogenous hormone estrogen
mixed agonists/antagonistics (agonistic in some tissues while antagonist in others) such
as tamoxifen (a SERM)
pure antagonists (antagonistic in all tissues) such as fulvestrant
The mechanism of mixed agonism/antagonism may differ:
depending on the chemical structure of the SERM, but, for at least for some
SERMs, it appears to be related to
the ratio of co-activator to co-repressor proteins in different cell types and
the conformation of the estrogen receptor induced by drug binding, which in turn
determines how strongly the drug/receptor complex recruits co-activators
(resulting in an agonist response) relative to co-repressors (resulting in
antagonism).
retention of nitrogen, Na, K, phosphorus
excretion of Ca
CHON anabolism
CHON catabolism
production of RBCs
Long acting depot forms; patch; oral
A/R:
Hirsutism
Deepening of voice
Oily skin
Weight gain
Decreased breast size
Testicular atrophy
DRUGS:
Prostaglandin alprostadil (caverject, muse)
Phosphodiesterase type 5 (PDE5)
Sildenafil (Viagra)
Tadalafil (cialis)
Vardenafil (levitra)
relax smooth muscles
filling of corpus cavernosum with blood

Onset: 27 minutes
Duration: 4 hours
C/I:
Priapism
Penile implants
Women
A/R:
Priapism
Fibrosis
rash
Male Contraception
Tried suppressing sperm production.
- Very unsuccessful.
- Most promising to date: testosterone enanthate + daily oral levonorgestrel; and
parenternalptestosteroneundecanoate + injectablemedroxyprogesteroneascetate. But,
- Highly variable results from clinical trials only ~ 60% of men became
azoospermic.
Significant adverse effects: acne, weight gain, polycythemia, potential increase in
prostate size.
back to the drawing board