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 Chemistry of Danazol
Danazol is a derivative of the synthetic hormone preparation that is related to testosterone. It has weak androgenic activity and no estrogenic or progestagenic effects.
The danzol molecule.
Mode of Action of Danazol
Danazol was approved by the U.S. Food and Drug Administration (FDA) as the first drug to specifically treat endometriosis in the early 1970s.
The observation that hyper androgenic states (an excess of male hormone) induce atrophy of the endometrium had led to the use of androgens in the treatment of endometriosis and danazol was one of these treatments put to the test. The efficacy of
danazol is based on its ability to produce a high androgen and low oestrogen environment which results in atrophy of the endometriotic implants and thus an improvement in pain. Treatment with danazol was effective in relieving painful symptoms related to endometriosis when compared to placebo. Laparoscopic scores were also improved with danazol treatment when compared with either placebo or no treatment. Side effects were more commonly reported in those patients receiving danazol than for placebo. Although effective for endometriosis, its use is limited by its masculinizing side effects. Its role as a treatment for endometriosis has been largely replaced by the
GnRH agonists. Unlike GnRH agonists, danazol
does not induce osteoporosis.
Luciano et al8101
studied the effects of danazol on pituitary and gonadal function
in seven normal women who volunteered to take danazol, 400 mg
twice daily, for 2 months. The amenorrhoeic state induced by
danazol was characterized by normal basal levels of
gonadotropins, prolactin, and estrogen. Serum androgen levels
were significantly increased as was the urinary excretion of
17-ketosteroids. These observations failed to support the
contention that danazol suppresses pituitary gonadotrophin
secretion or directly inhibits steroidogenesis. The results
suggested that danazol may have a primary site of action at the
ovary by suppressing the normal, orderly process of follicular
maturation.
Danazol (Danol Sanofi) has several modes of action. It tends to suppress the output of pituitary gonadotrophins (sex hormones) resulting in lowering of ovarian sex hormone production. It also reduces the effect of oestrogen and progesterone.
Though danazol prevents pregnancy particularly at higher
dosage, it is not licensed for use as a contraceptive agent.
Ovulation and cyclic bleeding usually return within 60 to 90
days when Danazol is discontinued.
Clinical Indications for Danazol
Danazol has been used in the treatment of:-
- endometriosis (endometriosis).
- heavy periods (menorrhagia - heavy periods).
- cyclical mastalgia (cyclical mastalgia).
- premenstrual syndrome (premenstrual syndrome).
- benign breast disease. In the treatment of fibrocystic breast disease, danazol usually produces partial to complete disappearance of nodularity and complete
relief of pain and tenderness. The total daily dosage of danazol for fibrocystic breast disease ranges from 100 mg to 400 mg taken in two divided doses depending upon patient response. Therapy should begin during menstruation. Otherwise, appropriate tests should be performed to ensure that the patient is not pregnant while on therapy with Danazol. Breast pain and tenderness are significantly relieved by the first month and eliminated in 2 to 3 months. Usually elimination of nodularity requires 4 to 6 months of uninterrupted danazol treatment.
Side Effects of Danazol
side effects include nausea, rashes, headache, visual disturbance, acne
weight gain and an increase in body hair but these are more common at high dose levels of 600 or 800mg daily.
Should any of these side effects occur, they usually rapidly
disappear when the danzol is discontinued. In practice,
danazol tends to be used when other medications are unsuccessful. Many patients have no problems with
danazol, particularly when it is used in low dosage, and it often improves symptoms.
Danazol tends to reduce the hormone fluctuations. Danazol 400mg daily will generally suppress the menstrual cycle and can be effective in PMS. Occasionally it may be effective at lower dose levels whilst some patients will need more.
Danazol can have adverse effect on a fetus so that ade quate contraception is essential.
As danazol may cause some degree of fluid retention, conditions that might be influenced by this factor, such as epilepsy, migraine, or cardiac or renal dysfunction, require careful observation.
Contraindications to danazol
Danazol is contraindicated in pregnancy because it
could masculinise a female fetus. Danazol is also
contraindicated when breast feeding.
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