STIROEL TABLETS

Indications

• Advanced hormone-dependent prostate cancer
• Hormone-responsive malignancies
• Postcoital contraception (historically)

Dosage

Adults: 250 mg three times a day, or as directed by a physician.

Mechanism of action

Estrogens, including diethylstilbestrol, diffuse into target cells and bind to estrogen receptors located in various tissues, such as the female reproductive tract, mammary glands, and the hypothalamus. This binding leads to the hepatic production of sex hormone-binding globulin (SHBG) and thyroid-binding globulin (TBG), while also suppressing follicle-stimulating hormone (FSH) from the anterior pituitary. DES may inhibit implantation of the fertilized ovum and suppress the hypothalamic-pituitary axis, resulting in decreased gonadotropin-releasing hormone (GnRH) secretion.

Pharmacodynamics

Diethylstilbestrol is a synthetic estrogen that mimics the effects of natural estrogens in the body. It promotes the development and maintenance of female secondary sexual characteristics and regulates the menstrual cycle. Due to its estrogenic properties, it can influence various physiological functions, such as reproduction and metabolism. However, its use has been linked to significant health risks, including cancers and reproductive issues in those exposed during pregnancy.

Pharmacokinetics

Diethylstilbestrol is rapidly absorbed when administered orally. It undergoes extensive first-pass metabolism, resulting in significant hepatic metabolism. The drug has a relatively long half-life, allowing for sustained action. It is primarily excreted via the kidneys. Caution is advised in patients with hepatic impairment, as the metabolism and clearance of the drug may be affected.

Contra-indications

• Do not initiate if serum transaminases greater than 2-3 times the upper limit of normal
• Acute porphyrias
• Severe hepatic impairment
• Pregnancy (first trimester)

Adverse effects

• Bone pain
• Breast abnormalities
• Cervical mucus increased
• Cholelithiasis
• Depression
• Erectile dysfunction
• Erythema nodosum
• Feminization
• Fluid retention
• Gynaecomastia
• Headaches
• Hypercalcaemia
• Hypertension
• Increased risk of thrombosis
• Jaundice
• Mood altered
• Nausea
• Skin reactions
• Sodium retention
• Testicular atrophy
• Uterine disorders
• Vomiting
• Weight changes
• Withdrawal symptoms
• Anxiety
• Alopecia
• Cardiovascular disorders
• Chest pain
• Constipation
• Dizziness
• Dyspnoea
• Insomnia
• Photosensitivity reactions
• QT interval prolongation

Interactions

• Caution advised with anti-androgens
• Avoid excessive alcohol consumption
• Increased susceptibility to QT-interval prolongation with other medications

Precautions

• Monitor liver function before starting treatment and monthly for the first four months
• Monitor bone mineral density before starting treatment, after one year, and as clinically indicated
• Caution in diabetes
• Caution in cardiac disease

Pregnancy

Use in pregnancy is contraindicated, especially in the first trimester due to risks of abnormalities in female offspring.

Breast-feeding

Caution is advised as Diethylstilbestrol may be excreted in breast milk.

Storage

Store in a cool, dry place away from direct sunlight and moisture.

Formulations

• Diethylstilbestrol 1 mg tablets

Mechanism of action

Estrogens diffuse into their target cells and interact with a protein receptor, the estrogen receptor. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. The effect of Estrogen binding their receptors causes downstream increases the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH). The precise mechanism(s) of action of DES as a postcoital contraceptive is not fully understood; however, the drug appears to inhibit nidation (implantation) of the fertilized ovum in the endometrium when administered within 72 hours following coitus. The postcoital contraceptive activity of the drug may involve effects mediated via decreased concentrations of circulating progesterone, effects on tubal motility resulting in accelerated passage of the ovum into the uterus, and inhibition of synthesis of carbonic anhydrase in the endometrium. ... DES ... inhibited the postcastration rise in plasma FSH amd LH levels ... . In addition, DES stimulated large increases in prolactin secretion ...

Pharmacodynamics

Diethylstilbestrol is a synthetic estrogen that was developed to supplement a woman's natural estrogen production. In 1971, the Food and Drug Administration (FDA) issued a Drug Bulletin advising physicians to stop prescribing DES to pregnant women because it was linked to a rare vaginal cancer in female offspring.