Endocrine effects of danazol in the treatment of endometriosis

Bevan, J. R.; Dowsett, Mitch; Jeffcoate, S. L.

doi:10.1111/j.1471-0528.1984.tb05901.x

Cited by 20 publications

(6 citation statements)

References 27 publications

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“…We have confirmed that administration of dana¬ zol is associated with a decrease in the serum con¬ centration of SHBG (21), probably due to inhibi¬ tion of hepatic synthesis of SHBG (22), and thus with a modest rise in the calculated free testoste¬ rone index. In vitro, testosterone stimulates (23), whereas insulin inhibits (24) the synthesis of SHBG.…”

Section: Discussionsupporting

confidence: 74%

Influence of danazol and goserelin on insulin and glucagon in non-obese women with endometriosis

Golland¹,

Vaughan-Williams²,

Shalet³

et al. 1990

Acta Endocrinologica

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To investigate the effects of medical treatment of endometriosis on concentrations of insulin and glucagon in comparison with those of androgens, 12 nonobese women with minimal endometriosis were randomly allocated to receive treatment with either danazol or the gonadotropin-releasing hormone analogue, goserelin. In subjects treated with danazol, mean (sd) summed serum insulin (1.08 (0.22) nmol/l pretreatment; 3.00 (1.50) nmol/l after treatment, p<0.05) and summed plasma glucagon (94 (21) pmol/l pretreatment; 238 (113) pmol/l after treatment, p<0.05) responses to oral glucose administration increased significantly, but remained unchanged in subjects treated with goserelin. In the danazol-treated group, the mean free testosterone index increased from 3.3 (1.6) to 13.3 (4.2) (p<0.01), but there was no correlation between either glucagon or insulin and free testosterone index. In the goserelin-treated subjects, however, there was no change in mean free testosterone indices (pretreatment 3.6 (1.0), post-treatment 3.9 (1.8). Thus, the increase in free testosterone index induced by danazol treatment is not responsible for the concomitant development of hyperinsulinaemia and hyperglucagonaemia.

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Section: Discussionsupporting

confidence: 74%

Influence of danazol and goserelin on insulin and glucagon in non-obese women with endometriosis

Golland¹,

Vaughan-Williams²,

Shalet³

et al. 1990

Acta Endocrinologica

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“…Indeed, it has been speculated that the therapeutic effect of danazol upon ectopic endometrium derives from the increased free androgen levels rather than from any antigonadotrophic action (Bevan et al 1984). Nonetheless, significant problems are apparent that make it unlikely they will replace existing contraceptive methods in most women.…”

Section: Conclusion and Future Prospectsmentioning

confidence: 99%

Clinical aspects of LHRH analogues in gynaecology: a review

McLachlan

Healy

Burger

1986

BJOG

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LHRH agonists are synthetic peptide analogues of hypothalamic luteinizing hormone releasing hormone (LHRH) with superior potency and longer duration of gonadotrophin release. Paradoxically, repeated administration causes pituitary desensitization with diminished gonadotrophin and oestradiol secretion. A state of hypogonadotrophic hypogonadism is reversibly induced; plasma oestrogen can be reduced to castrate levels. LHRH agonists reliably induce anovulation but are unlikely to replace existing contraceptive methods in most normal women. By contrast these agents offer, for the first time, the prospect of inducing a reversible pseudomenopause essentially free of side-effects. LHRH analogues promise to have a profound impact upon the management of a diverse range of oestrogen-dependent gynaecological diseases both benign and malignant. In particular, they may shortly become the gynaecological treatment of choice in endometriosis, as well as becoming part of the management of common gynaecological disorders such as dysfunctional uterine bleeding and uterine fibroids.

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“…Danazol, the 2 , 3 -~ isoxazol derivative of 17a-ethinyl testosterone (ethisterone), is widely used in the treatment of endometriosis on the basis of its supposed inhibition of gonadotrophin secretion (Sherins et al, 1971). Whilst it is well established that high dosages (above 400 mg per day) can suppress the mid-cycle LH surge and lead to cessation of menses, basal levels of LH and FSH are essentially unchanged in humans with intact gonadal function (Barbieri & Ryan, 1981;Bevan et al, 1984). Lower dosages ( c 200 mg per day) in most cases do not suppress cyclic menstruation but are nonetheless therapeutically effective (Biberoglu & Behrman, 198 1;Samaras et al, 1983).…”

mentioning

confidence: 99%

“…We have previously suggested that the androgenic activity of danazol in v i m may be at least partly dependent on its suppression of plasma sex hormone binding globulin (SHBG) levels (Bevan et al, 1984) which would be expected to result in an increase in the free, biologically active testosterone concentration. We have further confirmed that the percent free testosterone is significantly increased by danazol treatment (Dowsett et al, 19861, but total testosterone concentrations have been reported as decreased by some authors (Nilsson et al, 1983;Carlstrom et al.…”

mentioning

confidence: 99%

Dosage‐related Effects of Danazol on Sex Hormone Binding Globulin and Free and Total Androgen Levels

Forbes

Dowsett

Rose

et al. 1986

Clinical Endocrinology

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Danazol is known to cause marked suppression of sex hormone binding globulin (SHBG) levels in plasma and to increase the proportion of plasma testosterone unbound to protein but the effect on the concentration of total and free testosterone is unclear. Twenty-five patients with endometriosis were treated daily for 6 months with doses of danazol ranging from 50 to 600 mg. The fall in SHBG and rise in percent free testosterone was dose-related during the early part of treatment. Suppression of total testosterone and 5 alpha-dihydrotestosterone levels occurred and was probably due to increases in metabolic clearance rates. The observed fall in androstenedione levels was related to the incidence of menstrual abnormality, suggesting that this might be due to reduced ovarian activity. The concentration of free testosterone increased by a factor of two in the first week but subsequently returned to levels of between 25 and 50% above pretreatment levels. This pattern of changes may be due to the rise in metabolic clearance rates being dependent on induction of enzymes of androgen metabolism.

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Endocrine effects of danazol in the treatment of endometriosis

Cited by 20 publications

References 27 publications

Influence of danazol and goserelin on insulin and glucagon in non-obese women with endometriosis

Influence of danazol and goserelin on insulin and glucagon in non-obese women with endometriosis

Clinical aspects of LHRH analogues in gynaecology: a review

Dosage‐related Effects of Danazol on Sex Hormone Binding Globulin and Free and Total Androgen Levels

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