Danazol in the Treatment of Infertility

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Danazol treatment was found effective for endometriosis-associated infertility and habitual abortion, achieving pregnancy rates around 40% in both patient groups.

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This paper discusses the use of danazol in managing infertility, building on earlier observations of its anti-endometriotic effects. The author reports that danazol alleviated dysmenorrhoea, dyspareunia, and pelvic discomfort, and that after discontinuation a 40–50% pregnancy rate was observed; a separate 3-month course (200 mg daily) in women with unexplained infertility was said to result in roughly 40% achieving pregnancy within 6 months after stopping, and the author also describes a trial of 100 mg daily in habitual aborters with an outcome described as better than chance. A major caveat explicitly addressed is that placebo or other regimens can lead to conception in about 15–20% of infertile women, so the unusually good results with danazol are used to argue against a placebo effect. This paper is centrally about endometriosis — it frames danazol’s infertility effects as arising from its marked anti-endometrial effects and prior endometriosis experience.

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Abstract

Danazol, an interesting pharmacologic steroid 'in search of a disease', was first used by my group in the management of endometriosis because of the marked anti-endometrial effects found during clinical trials. The results in alleviating dysmenorrhoea, dyspareunia, and pelvic discomfort were surprisingly good, but more important was the 40 to 50% pregnancy rate that occurred following discontinuation of its use. In addition, because we suspected that women with unexplained infertility might be harbouring an occult or microendometriosis, a 3 month course of 200mg of danazol was tried in such patients, and proved effective in overcoming infertility in roughtly 40% of patients within 6 months after discontinuation of medication. We serendipitously found that some habitual aborters carried to term after a course of danazol. Accordingly, a trial of 100mg daily for 3 months was undertaken with a satisfactory outcome in more instances than could be attributed to chance alone. To readily appreciate the effectiveness of this agent, one must be aware that conceptions may follow the use of placebos or whatever regimen is employed in about 15 to 20% of infertile women. The unusually good results that we and other investigators in the field obtained with danazol rules out a placebo effect.
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Summary Danazol, an interesting pharmacologic steroid ‘in search of a disease’, was first used by my group in the management of endometriosis because of the marked anti-endometrial effects found during clinical trials. The results in alleviating dysmenorrhoea, dyspareunia, and pelvic discomfort were surprisingly good, but more important was the 40 to 50 % pregnancy rate that occurred following discontinuation of its use. In addition, because we suspected that women with unexplained infertility might be harbouring an occult or microendometriosis, a 3 month course of 200mg of danazol was tried in such patients, and proved effective in overcoming infertility in roughly 40% of patients within 6 months after discontinuation of medication. We serendipitously found that some habitual aborters carried to term after a course of danazol. Accordingly, a trial of 100mg daily for 3 months was undertaken with a satisfactory outcome in more instances than could be attributed to chance alone. To readily appreciate the effectiveness of this agent, one must be aware that conceptions may follow the use of placebos or whatever regimen is employed in about 15 to 20 % of infertile women. The unusually good results that we and other investigators in the field obtained with danazol rules out a placebo effect. Similar content being viewed by others References Audebert, A.J.M. and Emperaire, J.C.: Bilan du traitement de l’endometriose un antigonadotrope. Contraception-Fertilite-Sexualite 5: 731 (1977). Barbieri, R.L.; Canick, J.A.; Makris, A.; Todd, R.B.; Davies, I.J. and Ryan, K.J.: Danazol inhibits steroidogenesis. Fertility and Sterility 28: 809 (1977). Brosens, I.A.; Koninckx, P.R. and Corveleyn, P.A.: A study of plasma progesterone, oestradiol-17 Beta, prolactin and LH levels and of the luteal phase appearance of the ovaries in patients with endometriosis and infertility. British Journal of Obstetrics and Gynaecology 85: 246 (1978). Caudron, J.: Results of clinical and endocrinological investigation of danazol in gynaecological disorders. Benelux Symposium: Danatrol, p.81 (European Press, Ghent 1978). Colle, M.L. and Greenblatt, R.B.: Contraceptive properties of danazol. Journal of Reproductive Medicine 17: 98 (1976). Del Pozo, E.: Prolactin; in Greenblatt (Ed) Induction of Ovulation, p.93 (Lea & Febiger, Philadelphia 1979). Dmowski, W.P.: Endocrine properties and clinical application of danazol. Fertility and Sterility 31: 237 (1979). Dmowski, D.W. and Cohen, M.R.: Scientific exhibit: Endometriosis, current concepts in hormonal therapy using a new antigonadotropin (danazol). University of Chicago, Pritzker School of Medicine (1977). Dmowski, W.P. and Cohen, M.R.: Antigonadotropin (danazol) in the treatment of endometriosis: evaluation of post treatment fertility and three-year follow-up data. American Journal of Obstetrics and Gynecology 130: 41 (1978). Friedlander, R.L.: Experiences with danazol in therapy of endometriosis; in Greenblatt (Ed) Recent Advances in Endometriosis, Excerpta Medica. International Congress Series 368: 100 (1976). Geirregat, R.: Pharmacology and pharmacodynamics of danazol, a condensed survey of current knowledge. Benelux Symposium: Danatrol, p. 13 (European Press, Ghent 1978). Greenblatt, R.B. and Tzingounis, V.A.: Danazol treatment of endometriosis: Long-term follow-up. Fertility and Sterility 32: 518 (1979). Greenblatt, R.B.; Mahesh, V.B. and Pico, I.R.: Stimulation of ovulation in the human with clomiphene citrate; in Wood and Walters (Eds) Fifth World Congress of Gynecology and Obstetrics, Sydney, Australia, p.301 (Appleton-Century-Crofts, New York 1967). Greenblatt, R.B.; Dmowski, W.P.; Mahesh, V.B. and Scholer, H.F.L.: Clinical studies with an antigonadotropin-danazol. Fertility and Sterility 22: 102 (1971). Greenblatt, R.B.; Borenstein, R. and Hernandez-Ayup, S.: Experiences with danazol (an antigonadotropin) in the treatment of infertility. American Journal of Obstetrics and Gynecology 118: 783 (1974). Jenkin, G.: Letter to the Editor. Fertility and Sterility 31: 462 (1979). Jenkin, G.; Cookson, I.C.; Thorburn, G.D. and Robinson, J.S.: Action of danazol on steroid receptors of the human endometrium. Proceedings of the Endocrine Society of Australia 21: 54 (1978). Kistner, R.W.: Infertility with endometriosis: A plan of therapy. Fertility and Sterility 13: 237 (1962). Koninckx, P.R.; Brosens, I.A.; Vasquez, G. and Grodts, S.: Physiopathology and treatment of infertility in women with pelvic endometriosis. Benelux Symposium: Danatrol, p. 19 (European Press, Ghent 1978). Lunenfeld, B. and Conini, P.: Historic aspects of gonadotropins in the induction of ovulation; in Greenblatt (Ed) Ovulation, p. 105 (Lippincott, Philadelphia 1966). Manson, A.J.; Stonner, F.W.; Neumann, H.C.; Christiansen, R.G.; Clarke, R.L.; Ackerman, J.H.; Page, D.F.; Phillips, D.K.; Potts, G.O.; Arnold, A.; Beyler, A.L. and Clinton, R.O.: Steroidal heterocycles VII. Androstano (2, 3-d) isoxazoles and related compounds. Journal of Medicinal Chemistry 6: 1 (1963). Metler, L. and Seiz, E.: The application of danazol for the treatment of endometriosis genitalis externa — evaluation of 122 cases of endometriosis, diagnosed via pelviscopy. Treatment with thermocoagulation of endometriotic foci and danazol. Benelux Symposium: Danatrol, p. 109 (European Press, Ghent 1978). Schellen, A.M.C.M.: Danazol, a new horizon in the treatment of endometriosis. Benelux Symposium: Danatrol, p.73 (European Press, Ghent 1978). van Dijk, J.G.; Frolich, M.; Brand, E.C. and van Hall, E.V.: The ‘treatment’ of unexplained infertility with danazol. Fertility and Sterility 31: 481 (1979). Young, M.D. and Blackmore, W.P.: The use of danazol in the management of endometriosis. Journal of International Medical Research 5(Suppl. 3): 86 (1977). Author information Authors and Affiliations Rights and permissions About this article Cite this article Greenblatt, R.B. Danazol in the Treatment of Infertility. Drugs 19, 362–369 (1980). https://doi.org/10.2165/00003495-198019050-00006 Published: Issue date: DOI: https://doi.org/10.2165/00003495-198019050-00006

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Condition tags

endometriosisinfertility

MeSH descriptors

Danazol Infertility, Female Pregnadienes Abortion, Habitual Abortion, Habitual Clinical Trials as Topic Danazol Endometriosis Endometriosis Female Humans Infertility, Female Infertility, Female Infertility, Female Pregnadienes Pregnancy

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