(Female Sex hormones)

Natural estrogens- Estradiol is the major estrogen secreted by the ovary.

It is synthesized in the graafian follicle, corpus luteum and placenta from cholesterol

Synthetic estrogens - Natural estrogens are inactive orally and have a short duration of action due to rapid etabolism in liver. Synthetic compounds have been produced:

Steroidal- Ethinylestradiol, Mestranol, Tibolone.

Nonsteroidal- Diethylstilbestrol (stilbestrol) Hexestrol, Dienestrol

Regulation of secretion

Actions of estrogen

Sex organs: Growth of uterus, fallopian tube, and vagina

• Vaginal epithelium – thickened, stratified, cornified

• Responsible for the proliferation of endometrium in preovulatory phase

• Increase rhythmic contraction of fallopian tube and uterus

• Induce watery alkaline secretion from the cervix – favours sperm penetration

• Sensitizes uterus to oxytocin

• Deficiency of estrogen – atrophic changes

Secondary sex characters:

• Breast growth

• Pubic axillary hair

• Accumulation of fat

• Feminine body contours and behaviour are influenced

Metabolic effects – Anabolic (weaker than testosterone)

• Promotes fusion of epiphysis

• Maintains/ Prevents resorption and inhibition of osteoclast pit formation

• Expression of bone matrix proteins

• Promotes positive calcium balance

Other actions –

• Mild salt water retention

• Combination contraceptives - Impaired glucose tolerance

• Improved lipid profile

• Stimulate fibrinolytic activity

• Induce NO synthase – promote vasodilation

• Increases lithogenicity of bile and decrease bile salt secretion

Mechanism of action

• Estrogens bind to specific nuclear receptors in target cells and produce effects by regulating protein synthesis.

• Estrogen receptors (ERs) present in female sex organs, breast, pituitary, liver, bone, blood vessels, heart, CNS and in certain hormone responsive breast carcinoma cells

• The  ER is  analogous  to  other  steroid  receptors:  agonist  binding  to  the  ligand binding domain brings about receptor dimerization and interaction with ‘estrogen response elements’ (EREs) of target genes

• Gene transcription is promoted


• Natural – Inactive orally

• Bind to Steroid Hormone Binding Protein (SHBG)

• Estradiol gets converted to estrone in liver – estriol derived from estrone

• Glucuronide and sulfate conjugation

• Excreted urine and bile

• Enterohepatic circulation

• Transdermal estradiol: 5, 10 and 20 cm2 delivers 0.025, 0.05, 0.1 mg


• Males: Suppression of libido, gynacomastia, feminisation

• Early fusion of epiphyses in children

• Pregnant women:  Increase incidence of vaginal/ cervical carcinoma in female offspring

• Other genital abnormalities in male and female offspring

• Post-menopausal women:  increased risk of irregular bleeding and endometrial carcinoma

• Accelerate the growth of existing breast cancer


• As contraceptive

• In Hormone Replacement Therapy

• Senile vaginitis

• Delayed puberty in girls

• Dysmenorrhoea

• Acne

• Dysfunctional uterine bleeding

• Carcinoma prostrate

• Hirsutism


Clomiphene citrate

   Pure antagonist at estrogen receptor

   Inhibits estrogenic feedback – stimulates ovulation

   Used in sterility (Amenorrhoea, anovular cycles)

   ADR: Polycystic ovary, multiple pregnancy, risk of ovarian tumour

  To aid in vitro fertilization

   In men - Spermatogenesis

Selective Estrogen Receptor Modulators (SERMs)

   Tamoxifen citrate:  Potent estrogen antagonist in breast carcinoma cells, blood vessels

   Partial agonist at uterus, bone, liver, pituitary

   Toremifene: Newer congener of tamoxifen

   Raloxifene: Partial agonist at bone and CVS, Antagonist in endometrium, breast

   Ormeloxifene: Supress endometrial proliferation

Aromatase inhibitors

   Letrozole, anastrozole, exemestane

   Orally active

   Reversible inhibitor

   Early breast cancer: Adjuvant therapy after mastectomy in ER +ve cases

   Advanced breast cancer

   ADR: Dyspepsia, thinning of hair, joint pain, risk of thromboembolism


These are substances which convert the estrogen primed endometrium to secretory and maintain pregnancy (Progestin = favouring pregnancy)

Natural progestin Progesterone, a 21 carbon steroid, is the natural progestin

• Derived from cholesterol.

• Secreted by the corpus luteum  (10–20 mg/day) in the later half of menstrual cycle under the influence of LH

• Production declines a few days before the next menstrual flow

• If the ovum gets fertilized and implants—the blastocyst mmediately starts producing chorionic gonadotropin which is absorbed and sustains the corpus luteum  in early pregnancy.

• Placenta starts secreting lots of estrogens and progesterone from 2nd trimester till term.

Synthetic progesterone

• Progesterone derivatives (21C) - Medroxy progesterone acetate, megestrol acetate, dihydrogesterone, hydroxyl progesterone caproate, nomegestrol acetate

• 19 – Nortestosterone derivative (18C)Norethindrone (Norethisterone), lynestrenol (ethinyl estrenol), allyl estrenol, levonorgestrel (Gonane)

• Newer compounds - Desogestrel, norgestimate, gestodene

Actions of estrogen


• Preparation of uterus for nidation and maintenance of pregnancy

• Prevention of endometrial shedding, decrease uterine motility, inhibition of immunological rejection of foetus

• Secretory changes in estrogen primed endometrium, hyperemia, tortuocity of glands

• Decreases sensitivity of myometrium to oxytocin


Progesterone converts the watery cervical secretion induced by estrogens to viscid, scanty and cellular secretion which is hostile to sperm penetration


Induces pregnancy like changes in the vaginal mucosa—leukocyte infiltration of cornified epithelium


• Progesterone causes proliferation of acini in the mammary glands

• Along with estrogens, it prepares breast for lactation

• Withdrawal of these hormones after delivery causes release of prolactin from pituitary and milk secretion starts


High circulating concentration of progesterone (during pregnancy) appears to have a sedative effect

Body temperature: Slight increase (Hypothalamus thermostat) Respiration: High dose stimulate respiration

Metabolism: Progestins with androgenic effect increase LDL, decrease HDL Pituitary: Weak inhibitor of Gonadotropin secretion

• Hypothalamus decreases the frequency of LH pulses

• Prevents LH surge and ovulation


• Orally high FPM

• Liver – Pregnanediol

• Glucuronic acid and sulfate conjugation

• Synthetis progestins

– Orally active

– Metabolised slowly

– Half-life: 8 – 24 hrs


• Breast engorgement, headache, rise in BT, edema, esophageal reflux, acne, mood swings

• Continuous: Irregular bleeding/ amenorrhoea

• 19 nor derivatives – atherogenesis

• In HRT – Increased risk of breast cancer

• Blood sugar – raise with potent agents

• Early pregnancy – Masculinization of female foetus and other congenital abnormalities


• As contraceptive


• Dysfunctional uterine bleeding

• Endometriosis

• Premenstrual syndrome

• Threatened/ habitual abortion

• Endometrial carcinoma

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