Anti-Oestrogens
Introduction:
- The drugs which antagonize oestrogens at the receptor level are clomiphene and tamoxifen
Clomiphene Citrate:
- Nonsteroidal compound related to diethylstilbestrol (DES)
Mixture of two isomers:
- zuclomiphene(Cis 38%)+enclomiphene citrate(trans 63%)
Mode of Action:
- DOC in induction of ovulation.
- Starting on the second day of the cycle and given for 5 days
Blocks the negative feedback of oestrogen at hypothalamus by binding estrogen receptor
↓
GnRH release
↓
LH & FSH secretion
- Exerts anti-E action on the endometrium and cervical mucus & decrease in the fertility rate.
- E2 level starts increasing 5–6 days after stopping drug and induces maturity of the Graafian follicle & ovulation with LH surge.
Indications:
Anovulatory infertility.
- Polycystic ovarian syndrome
- In in vitro fertilization:Gamete intrafallopian transfer (GIFT) technique and assisted reproduction therapy(ART).
- Stein- leventhal syndrome
- 25 mg orally for 25 days each month for 3 to 6 months to stimulate spermatogenesis(used for male infertility with oligozoospermia)
Contraindications
- Ovarian cyst—the cyst can increase in size.
- Chronic liver disease, because it is metabolized in the liver.
- Scotoma.
Side Effects
- Ovarian enlargement
- Hot flushes, sweating due to oestrogen deficiency
- Osteoporosis
- Nausea, vomiting
- Visual disturbances, blurring,scotoma
- Headache, dizziness
- Urticaria
- Hair loss
- Weight gain
- Anti-oestrogenic effect on cervical mucus and endometrium
- CLPD
- Ovarian Hyperstimulation Syndrome(OHSS)
- Neural tube defect
- Multiple ovulation and multiple pregnancy(6-10%)
- Abortion rate 25 to 40%
- Ovarian malignancy( treatment is extended beyond 1 year)
- Premature ovarian failure
- Gynaecomastia
- Increase Incidence of unruptured luteinized follicle
Letrozole:
- Nonsteroidal aromatase inhibitor
- Induce ovulation
- Prevents conversion of androstenedione to oestrone
Advantages over clomiphene:
- Better pregnancy rate:no anti-oestrogenic action on the endometrium & cervix
- Induces mono-follicular stimulation, adequate LH surge and avoids multiple pregnancy
- Better implantation
- No hyperstimulation syndrome
- Cause drowsiness and liver dysfunction.
Tamoxifen:
- Nonsteroidal anti-oestrogenic drug
- selective estrogen receptor modulator (SERM).
- Acts by binding to and reducing the availability of oestrogen receptors.
Dosage:
- 10–20 mg twice daily for less than 5 yrs
Uses:
- Advanced breast cancer in postmenopausal women:BRCA1 and BRCA2 gene positive women
- PCOD.
Side effects:
- Hot flushes, vaginal dryness (anti-E2 action)
- Endometrial hyperplasia, polyp
- Endometrial carcinoma and sarcoma
- Hyperglyceridaemia,
- Deep venous thrombosis
- Ischaemic heart disease
- Retinopathy, Cataract
Precautions:
- Monitor endometrial growth
- Women receiving Tamoxifen should be periodically screened with Endometrial sampling
Ormeloxifene (Centchroman)
- Nonsteroidal anti-oestrogen developed for its contraceptive potential.
- Weekly nonsteroidal pill
- Antioestrogen activity on endometrium
- Does not inhibit ovulation and exerts contraceptive effect on implantation.
Exam Question
- Antihormonal substance used to induce ovulation clomiphene citrate
- Anovulatory infertility can be treated by clomiphene
- Clomiphene citrate is indicated in stein- leventhal syndrome
- Clomiphene causes hyperstimulation
- Drugs used for ovulation induction Clomiphene citrate & Tamoxifen
- Clomiphene citrate is Anti estrogen
- The most serious complication of clomiphene therapy for induction of ovulation is Hyperstimulation syndrome
- Tamoxifen is Non steroidal antioestrogenic
- Long term tamoxifen therapy may cause Endometrium Ca
- In Clomiphene citrate Risk of multiple pregnancy is 6-10%
- Clomiphene citrate can also be used for male infertility with oligozoospermia
- Gynaecomastia is caused by Clomiphene citrate
- Mechanism of action of Clomiphene Citrate is Binds estrogen receptors and prevents negative feed back at hypothalamus
- Side effects of clomiphene citrate include Multiple pregnancy, Increase risk of ovarian ca & Multiple polycystic ovary
- Women receiving Tamoxifen should be periodically screened with Endometrial sampling
- Use of tamoxifen in carcinoma of breast patients shows Endometrial hyperplasia,Thromboembolic events, Endometrial Carcinoma & cataract
- Tamoxifene is SERM
- Letrozole belongs to Aromatse inhibitors
- Drug useful in breast cancer is Tamoxifen
Don’t Forget to Solve all the previous Year Question asked on Anti-Oestrogens
