Sex Hormones, Derivatives and Antagonists:

Estrogen
-Primary sex hormone.
-Regional proliferation of alveolar.
-Proliferation of endometrial cells  thick lining.
-Undergoes last first pass metabolism.
-Natural: 17-B-estradiol, estrone, estriol.
-Synthetic: ethinyl estradiol, mestranol.
-Ethinyl substitution increases oral potency: undergoes less first pass metab.
-Transported bound to Sex Hormone Binding Globulin (SHBG) – natural, and albumin – synthetic.
-FSH produces the follicle.
-LH responsible for the surge of estrogen + progesterone + release of the follicle.

-Proliferative Phase: Estrogen dominates  prepares body for pregnancy (proliferation).

-Secretory Phase: Progesterone dominates maintains pregnancy.

Effects of Estrogen:
1. Metabolic Effects:
 Bone Mass: ↓ bone loss - ↓ bone resorption  stops osteoclasts from breaking down.
 Lipid Metabolism: ↑ HDL and ↓ LDL.
 Carbohydrate Metabolism: Diabetes- ↓ glucose tolerance.
 Protein Metabolism: ↑ SHBG: ↑ protein transport = more estrogen transported.
 Blood: ↓ antithrombin III levels = ↑ blood clotting – risk of thrombus.
 CVS: ↓ arteriolar vasodilation.
 Skin: ↓ sebum production: ↓ oil – pill can be used for acne.
 Gall Bladder: ↑ cholesterol in bile, ↑ risk – saturates blood in bile – concentrated bile/gall stones.
2. Routes of Administration:
 Oral. Parenteral, transdermal, topical.
 Lipophillic (non-polar).
 Absorption from GIT: rapid.
 Transdermal: slow, sustained, high levels do not enter liver.
 Injection: oil-based, ↓ absorption rate and ↑ duration of action.
 T + I: more potent and longer t1/2
3. Adverse Effects:
 N, V
 Fullness and tenderness of breast + oedema.
  Migraine.
 Reactive/excaberate endometriosis.
 Gall bladder disease (↑ gall stones).
 Thromboembolism (↑ clotting).
 Carcinogenic actions: endometrial cancer, breast cancer.
 Glucose Intolerance
4. Hormone Replacement Therapy: For someone who is not producing enough estrogen.
 Estrogen Monotherapy hysterectomy
 Combined Continuous:
-Progestin added daily.
-Prevents endometrial proliferation.
-Avoids bleeding.
 Combined Sequential:
-Progestin added for the last 10-14 days of the cycle.
-Produce endometrial shedding and withdrawal bleeding.

ESTROGEN THERAPY
Indications C/I Cautions Monotherapy Parenteral Estrogen + Progestin (Combination).
Estrogen
-Osteoporosis -Breast cancer. -Diabetes. -Mainstay of therapy. -Bypasses 1st -In women with an intact uterus.
↓ bone resorption pass effect.
Prevent bone loss. -Past DVT or - -Hysterectomy: -Minimal effect -Cyproterone, drospirenone,
-Urogenital Atrophy: pulmonary Hypercholesterolaemia. Progesterone on blood. medrogestrone,
Dryness and itching of the vagina, embolism. unfavourably alter HDL: -Transdermal medroxyprogesterone,
painful intercourse and urination, -Hypertension. LDL ratio. patches. norethisterone.
sudden/expected -Active liver -SC implants.
urinary incontinence. disease. -Preparations available: -Vaginal -Transdermal estradiol/
-Vasomotor Symptoms: Conjugated pessaries (oil Norethisterone.
Hot flushes, chilly sensations, estrogens. based).
inappropriate sweating and paresthias. Estradiol -Rings.
Estriol -Topical gel
HRT EFFECTIVELY DECREASES THESE Estrone. applications.
SYMPTOMS.

Types of Progestins
 Progesterone:
 Medroxyprogesterone acetate.
 17 a-hydroxyprogesterone derivatives:
 Cyproterone : anti-andorgenic effects.
 Gonanes:
 Levonorgestrel : most androgenic
 Newer Gonanes:
 Drospirenone
General
-Testosterone + other androgens.
-Testosterone is produced in Leydig cells in
men and in the corpus luteum + adrenal
cortex in females.
 LH Steroidogenesis (production
of testosterone) Leydig cells.
 FSH Spermatogenesis.
-↓ Testosterone in males = infertility +
fatigue.
PROGESTINS
Physiological Effects Absorption, fate, excretion
-Development of a secretory endometrium. -Progesterone: rapid first pass metab.
-Abrupt ↓ in release of progestin from corpus luteum -MPA: injection/oral binds primarily to albumin.
at the end of the cycle menstruation. -19-norethisterone: good oral activity: bind to SHBG
-Cervical mucous = more viscous. and albumin.
-Maintenance of pregnancy. -Metabolised in liver.
-↑ T: during ovulation (0.2-0.3) -Used in contraception, HRT.
-May have depressant/hypnotic effects (opp from -Luteal phase is lengthened to treat: infertility,
estrogen). premature labour: Short luteal phase = egg did not
-↑ fat deposition. implant properly.
Progesterone:
1. Ovulation.
2. Proliferation of cells to become secretory.
ANDROGENS
Reaction Uses A/E
-TestosteroneDihydrotestosterone + -Male hypogonadism (low -Excessive masculinisation.
estradiol androgenic levels) -↓ Sperm production (long-term
= Enzyme: 5α reductase (testosterone is -Aplastic anaemia use), testicular size.
metabolised) -Osteoporosis. -Gynaecomastia.
-Dihydro = more potent than testosterone. -Puberty for testosterone deficient -Virilisation in females.
boys. -Hepatooxic.
-Andosterone, adrostenedione, androstenediol -↑ athlete performance.
= low activity.
TOO MUCH Dihydro= balding + increased oil Testosterone Causes:
production. -Beard + body hair growth.
-Promotes the growth of the
prostate gland.
-Contributes to male sexuality.
-Bone + muscle growth.
 Hormone Replacement Therapy

ESTROGEN
Name of Drug MOA Indications S/E’s C/I’s and D/I’s Kinetics Extra Notes
-↑ risk of DVT and
pulmonary embolism.
-↓ total
-Hot flushes.
cholesterol, LDL ↓.
-Vagina -Undergoes
1. Tamoxifen -Estrogen dependant No ↑ in HDL and
dryness/discharge. enterohepatic
2. Toremifene breast cancer. triglycerides.
-Cataracts. circulation.
-Nausea.
-Estrogenic: in bone,
endometrium and blood.
-Anti-estrogenic: breast.
-↓ Total Cholesterol.
-↓ LDL. HLD is
unchanged.
-Selective estrogen -No stimulus on breast
receptor modulators. tissue and
-Tissue selective activity. endometrium
Advantage: lower risk of
-Hot flushes. endometrial cancer.
-Treatment of breast
-Leg cramps -DOES NOT alleviate
cancer.
3. Raloxifen -↑ risk of DVT and vasomotor symptoms.
-Prevention and treatment
pulmonary
of Osteoporosis.
embolism. -Estrogenic: in bone +
blood.
-Anti-Estrogenic: in breast
tissue.

-Agonist in bone distal

sites and spinal column.

-Estrogenic.
-HRT and endometriosis. -Progestogenic.
-Relieve in hot flushes, -Weak androgenic
insomnia, vaginal dryness, -NOT C/I in activity.
4. Tibolone
prevent bone loss. endometriosis!
-↓ breast pain, irregular -Less stim effect on
vaginal bleeding. endometrium anti-
estrogenic.
 -Ovarian
hyperstimulation.
-Antagonist in all tissues. -To produce more
-↑ incidence of
hormones.
-Infertility multiple births.
5. Clomiphene -Binds to estrogen -Ovarian stimulant.
-Used in conjunction with -Ovarian cysts.
(Antiestrogen) receptors in ovary- ↑ -Anti-estrogenic: in all
hCG. -Blurred vision.
estrogen (hypothalamus tissues.
-Acidic mucous.
 pituitary gland). -Tricks body.
-↑ Hot flushes.

-Estrogen receptor
-Hormone receptor
antagonist.
6. Fulvestrant positive metastatic breast -Admin: injection.
-Estrogen receptor
cancer.
downregulator.
-Continuous admin of
GnRH, long-acting GnRH
agonists.
7. Estrogen
-Inhibits ovarian synthesis
synthesis -Endometriosis + fibroids.
of estrogen. -Pulsatile: ↑ Hormones.
inhibitors
-Non-pulsatile: ↓
Hormones.
-Hypoestrogenic
8. Non-steroidal
-Aromatase: converts State:
aromatase
testosterone to estradiol.
inhibitors:
-Inhibit Aromatase enzyme: -Breast cancer. -Insomnia.
Anastrozole
↓ Estrogen  ↓ breast -Vaginal dryness
Letrozole
cancer risk. -Hot flushes
Exemestane
-Mood swings.
PROGESTINS
-Avoid use of NSAIDS.
-↑ uterine PG and
-Termination of pregnancy.
-Competitive antagonist of -Severe bleeding. sensitizes myometrium to
ANTIPROGESTINS -To induce labour.
both progesterone -Abdominal pain. contractile action.
-Treatment of
andglucocorticoid binding -Uterine cramps. -Used in conjunction with
Mifepristone endometriosis and breast
to the receptor. -N, V, D prostaglandin
cancer.
(Misoprostol) admin 48
hrs later.
ANDROGENS
TESTOSTERONE C/I: -Implant. -May cause premature
-Breast -Metabolised in the liver. closure of epiphyses if
-Prostate. -Undergoes very high admin early in puberty.
-Neoplasm. first pass metab. -Stimulates endogenous
 Cancer:
testosterone
feeds on cancer
cells.
D/I:
-↓effects of erythropoietin
Warfarin- ↑ production.
bleeding.
-May ↓ blood
glucose levels
(tolerance to
glucose).
TESTOSTERONE ESTERS
-Enanthate: used by
-Improve sexual -Bypass the liver.
sportsmen to ↑ muscle
Testosterone performance. -Deep IM injection = >
mass: ↑ RBC’s = more
Undecanoate, Enanthate, -Libido. bioavailability.
O2.
Cypionate
-17-α-alkyl derivative.
-DO NOT use for
prolonged periods.
-BOTH: androgenic +
-Oral bioavailability >
anabolic effects.
-Treat men with a -Hepatotoxic than testosterone.
METHYLTESTOSTERONE -Androgenic: ↑
testosterone deificency. prolonged periods.
steroidogenesis.
-Metab by the liver.
-Anabolic: ↑ muscle
growth.
-Only give androgens for
3-6months.
-NOT METAB TO
-In patients with hepatic
TESTOSTERONE ESTROGEN (adv) : End
disease and those with -CHRONIC USE: inhibition
DERIVATIVE product =
estrogenic symptoms of of spermatogenesis = ↑
dihydrotestosterone.
other testosterone infertility.
Mesterolone -Oral bioavailability >
.
than testosterone.
Nadrolone -Osteoporosis. -Erectile dysfunction. -Converted via 5-α
-Aplastic anaemia. -CV damage. reductase to
-↓ LH levels. Dihydronandrolone.
-Liver tumours.
-Cholestatic -↑ muscle growth,
jaundice. appetite, RBC production
and bone density.

-Binds to estrogen
ANTIGONADOTROPIN
receptors: inhibits
gonadotropin secretion
Danazol
exact MOA unknown.
ANTIANDROGENS Inhibitors of Testosterone
synthesis  androgen
receptor antagonist.
ANDROGEN RECEPTOR
-Potent androgen receptor
ANATGONISTS
antagonist.
Flutamide
-Aldosterone inhibitor
weak inhibitor of androgen
Spronolacotne
receptor weak inhibition
of testosterone synthesis.
-Potent androgen receptor
blocker.
Cyproterone Acetate
-Anti-androgenic (Strong).
5-α REDUCTASE
-Blocks conversion of
INHIBITORS
testosterone to
dihydrotestosterone.
Finasteride
GnRH ANALOGUES
-Controls release of FSH +
LH.
Goserelin
-Reduced liver toxicity.
-Larger Doses:
gynaecomastia, ↓ libido.
-Higher anabolic but
decreased androgenic
effects.
-Give for 3-6 months.
Causes: -Supresses FSH + LH.
-Greasy skin. -Weak progestational,
-Endometriosis.
-Acne. androgenic ad
-Breast dysplasia. -Metab in the liver.
-Voice changes. glucocorticoid activities.
-Gynaecomastia.
-Weight gain. -Induces endometrial
-Virilisation. atrophy.
-GnRH analogues inhibit
-Prostatic cancer. testosterone synthesis by
inhibiting LH secretion.
-GnRH analogue treat
metastatic prostate cancer. -Block action of adrenal
-Hepatotoxic.
-Female hirsutism andorgens.
excess body hair.
-K sparing diuretic.
-↓ Hirsuitism. -Weight gain.
C/I: Pregnancy -Has progestogenic
-Severe acne (↓ sebum -↓ Libido.
tetratogenic. property.
production). -Dry vagina.
-Benign prostatic
hyperplasia + prostate
-Infrequently causes
cancer. -Gynaecomastia.
impotence.
-Male pattern baldness,
hirsutism.
-Endometriosis (↓ -Headache. -Chronic/sustained
proliferation). -Depression admin.
-Breast and prostate -Hot flushes. = ↓ Hormone levels
cancer. -Vaginal dryness. -↑ FSH + LH = negative
-Dysfunctional uterine feedback.
bleeding.
 -Advanced prostate cancer.
-Central Precocious
puberty (CPP)- children
Triptorelin undergoing early puberty.
-Endometriosis.
-Infertility (pulsatile – not
frequently)
↓ testosterone -Advanced and metastatic
Buserelin
production. prostate cancer.
-Depot injection.
-Ovarian hyper-
stimulation. -Analogues = more
-Infertility: rather take
-Headache. potent + prolonged DOA
testosterone directly.
-Mood disorders. ( 3hrs vs 4mins)
-Visual disturbances.
-Pulsatile vs Non-
-Hot flushes. pulsatile admin.
-Loss of libido.