Skip to main content
Erschienen in: Archives of Gynecology and Obstetrics 3/2017

29.06.2017 | Review

“Per vaginam” topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review

verfasst von: Laura Buggio, Caterina Lazzari, Ermelinda Monti, Giussy Barbara, Nicola Berlanda, Paolo Vercellini

Erschienen in: Archives of Gynecology and Obstetrics | Ausgabe 3/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose

We aim to provide a comprehensive overview of the role of the vagina as a route for drug delivery and absorption, with a particular focus on the use of vaginal hormonal compounds for the treatment of deep infiltrating symptomatic endometriosis.

Methods

A MEDLINE search through PubMed was performed to identify all published studies in English language on vaginal hormonal treatments for symptomatic endometriosis.

Results

Main advantages of the vaginal route include avoidance of the hepatic-first pass metabolic effect, the possibility of using lower therapeutic dosages, and the reduction of side effects compared with the oral administration. Studies on endometriosis treatment mainly focused on the use of vaginal danazol (n = 6) and the contraceptive vaginal ring (n = 2). One pilot study evaluated the efficacy of vaginal anastrozole in women with rectovaginal endometriosis. Most investigations evaluated the vaginal use of hormonal agents in women with deep infiltrating endometriosis/rectovaginal endometriosis. Overall, a substantial amelioration of pelvic pain symptoms associated with endometriosis was observed, particularly of dysmenorrhea. A significant reduction in rectovaginal endometriotic nodule dimensions measured at ultrasound examination was detected by some but not all authors.

Conclusions

The vaginal route represents a scarcely explored modality for drug administration. High local hormonal concentrations might achieve a greater effect on endometriotic lesions compared with alternative routes. Future studies should focus on the use of the vagina for delivering target therapies particularly in patients with deeply infiltrating rectovaginal lesions.
Literatur
1.
Zurück zum Zitat Lete I, Luis Dueñas JL, Esplugues JV, Marti-Cabrera M (2010) Is the vagina an adequate route for the administration of hormonal contraceptives? Curr Drug Metab 11:839–849CrossRefPubMed Lete I, Luis Dueñas JL, Esplugues JV, Marti-Cabrera M (2010) Is the vagina an adequate route for the administration of hormonal contraceptives? Curr Drug Metab 11:839–849CrossRefPubMed
2.
Zurück zum Zitat Macht DI (1918) The absorption of drugs and poisons through the vagina. J Pharmacol Pathol 10:509–522 Macht DI (1918) The absorption of drugs and poisons through the vagina. J Pharmacol Pathol 10:509–522
3.
Zurück zum Zitat Alexander NJ, Baker E, Kaptein M, Karck U, Miller L, Zampaglione E (2004) Why consider vaginal drug administration? Fertil Steril 82:1–12CrossRefPubMed Alexander NJ, Baker E, Kaptein M, Karck U, Miller L, Zampaglione E (2004) Why consider vaginal drug administration? Fertil Steril 82:1–12CrossRefPubMed
6.
Zurück zum Zitat Hefler LA, Grimm C, van Trotsenburg M, Nagele F (2005) Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril 84:1033–1036CrossRefPubMed Hefler LA, Grimm C, van Trotsenburg M, Nagele F (2005) Role of the vaginally administered aromatase inhibitor anastrozole in women with rectovaginal endometriosis: a pilot study. Fertil Steril 84:1033–1036CrossRefPubMed
8.
Zurück zum Zitat Chapron C, Fauconnier A, Dubuisson JB, Barakat H, Vieira M, Bréart G (2003) Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease. Hum Reprod 18:760–766CrossRefPubMed Chapron C, Fauconnier A, Dubuisson JB, Barakat H, Vieira M, Bréart G (2003) Deep infiltrating endometriosis: relation between severity of dysmenorrhoea and extent of disease. Hum Reprod 18:760–766CrossRefPubMed
9.
Zurück zum Zitat Practice Committee of the American Society for Reproductive Medicine (2014) Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril 101:927–935CrossRef Practice Committee of the American Society for Reproductive Medicine (2014) Treatment of pelvic pain associated with endometriosis: a committee opinion. Fertil Steril 101:927–935CrossRef
10.
Zurück zum Zitat Cicinelli E (2008) Intravaginal oestrogen and progestin administration: advantages and disadvantages. Best Pract Res Clin Obstet Gynaecol 22:391–405CrossRefPubMed Cicinelli E (2008) Intravaginal oestrogen and progestin administration: advantages and disadvantages. Best Pract Res Clin Obstet Gynaecol 22:391–405CrossRefPubMed
11.
Zurück zum Zitat De Ziegler D, Bulletti C, De Monstier B, Jääskeläinen AS (1997) The first uterine pass effect. Ann N Y Acad Sci 828:291–299CrossRefPubMed De Ziegler D, Bulletti C, De Monstier B, Jääskeläinen AS (1997) The first uterine pass effect. Ann N Y Acad Sci 828:291–299CrossRefPubMed
12.
Zurück zum Zitat Katz DF, Dunmire EN (1993) Cervical mucus: problems and opportunities for drug delivery via the vagina and cervix. Adv Drug Deliv Rev 11:385–401CrossRef Katz DF, Dunmire EN (1993) Cervical mucus: problems and opportunities for drug delivery via the vagina and cervix. Adv Drug Deliv Rev 11:385–401CrossRef
13.
Zurück zum Zitat Pschera H, Hjerpe A, Carlstrom K (1989) Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17β and progesterone in postmenopausal women. Gynecol Obstet Invest 27:204–207CrossRefPubMed Pschera H, Hjerpe A, Carlstrom K (1989) Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17β and progesterone in postmenopausal women. Gynecol Obstet Invest 27:204–207CrossRefPubMed
14.
Zurück zum Zitat Vermani K, Garg S (2000) The scope and potential of vaginal drug delivery. Pharm Sci Technol Today 3:359–364CrossRefPubMed Vermani K, Garg S (2000) The scope and potential of vaginal drug delivery. Pharm Sci Technol Today 3:359–364CrossRefPubMed
15.
Zurück zum Zitat Villanueva B, Casper RF, Yen SS (1981) Intravaginal administration of progesterone: enhanced absorption after estrogen treatment. Fertil Steril 35:433–437CrossRefPubMed Villanueva B, Casper RF, Yen SS (1981) Intravaginal administration of progesterone: enhanced absorption after estrogen treatment. Fertil Steril 35:433–437CrossRefPubMed
16.
Zurück zum Zitat Mulders TM, Dieben TO (2001) Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertil Steril 75:865–870CrossRefPubMed Mulders TM, Dieben TO (2001) Use of the novel combined contraceptive vaginal ring NuvaRing for ovulation inhibition. Fertil Steril 75:865–870CrossRefPubMed
17.
Zurück zum Zitat Timmer CJ, Mulders TM (2000) Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet 39:233–242CrossRefPubMed Timmer CJ, Mulders TM (2000) Pharmacokinetics of etonogestrel and ethinylestradiol released from a combined contraceptive vaginal ring. Clin Pharmacokinet 39:233–242CrossRefPubMed
18.
Zurück zum Zitat van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC (2005) Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 72:168–174CrossRefPubMed van den Heuvel MW, van Bragt AJ, Alnabawy AK, Kaptein MC (2005) Comparison of ethinylestradiol pharmacokinetics in three hormonal contraceptive formulations: the vaginal ring, the transdermal patch and an oral contraceptive. Contraception 72:168–174CrossRefPubMed
19.
Zurück zum Zitat Roumen FJ, Dieben TO (2006) Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive. Fertil Steril 85:57–62CrossRefPubMed Roumen FJ, Dieben TO (2006) Comparison of uterine concentrations of ethinyl estradiol and etonogestrel after use of a contraceptive vaginal ring and an oral contraceptive. Fertil Steril 85:57–62CrossRefPubMed
20.
Zurück zum Zitat Dogterom P, van den Heuvel MW, Thomsen T (2005) Absence of pharmacokinetic interactions of the combined contraceptive vaginal ring NuvaRing® with oral amoxicillin or doxycycline in two randomised trials. Clin Pharmacokinet 44:429–438CrossRefPubMed Dogterom P, van den Heuvel MW, Thomsen T (2005) Absence of pharmacokinetic interactions of the combined contraceptive vaginal ring NuvaRing® with oral amoxicillin or doxycycline in two randomised trials. Clin Pharmacokinet 44:429–438CrossRefPubMed
21.
Zurück zum Zitat Verhoeven CH, van den Heuvel MW, Mulders TM, Dieben TO (2004) The contraceptive vaginal ring, NuvaRing®, and antimycotic co-medication. Contraception 69:129–132CrossRefPubMed Verhoeven CH, van den Heuvel MW, Mulders TM, Dieben TO (2004) The contraceptive vaginal ring, NuvaRing®, and antimycotic co-medication. Contraception 69:129–132CrossRefPubMed
22.
Zurück zum Zitat Landgren BM, Aedo AR, Johannisson E, Cekan SZ (1994) Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 μg/24 hours: a pilot study. Contraception 49:139–150CrossRefPubMed Landgren BM, Aedo AR, Johannisson E, Cekan SZ (1994) Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 μg/24 hours: a pilot study. Contraception 49:139–150CrossRefPubMed
23.
Zurück zum Zitat Landgren BM, Johannisson E, Masironi B, Diczfalusy E (1979) Pharmacokinetic and pharmacodynamic effects of small doses of norethisterone released from vaginal rings continuously during 90 days. Contraception 19:253–271CrossRefPubMed Landgren BM, Johannisson E, Masironi B, Diczfalusy E (1979) Pharmacokinetic and pharmacodynamic effects of small doses of norethisterone released from vaginal rings continuously during 90 days. Contraception 19:253–271CrossRefPubMed
24.
Zurück zum Zitat Landgren BM, Oriowo MA, Diczfalusy E (1981) Pharmacokinetic and pharmacodynamic studies with vaginal devices releasing norethisterone at a constant, near zero order. Contraception 24:29–44CrossRefPubMed Landgren BM, Oriowo MA, Diczfalusy E (1981) Pharmacokinetic and pharmacodynamic studies with vaginal devices releasing norethisterone at a constant, near zero order. Contraception 24:29–44CrossRefPubMed
25.
Zurück zum Zitat Igarashi M (1990) A new therapy for pelvic endometriosis and uterine adenomyosis: local effect of vaginal and intrauterine danazol application. Asia Oceania J Obstet Gynaecol 16:1–12CrossRefPubMed Igarashi M (1990) A new therapy for pelvic endometriosis and uterine adenomyosis: local effect of vaginal and intrauterine danazol application. Asia Oceania J Obstet Gynaecol 16:1–12CrossRefPubMed
26.
Zurück zum Zitat Igarashi M, Iizuka M, Abe Y, Ibuki Y (1998) Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis. Hum Reprod 13:1952–1956CrossRefPubMed Igarashi M, Iizuka M, Abe Y, Ibuki Y (1998) Novel vaginal danazol ring therapy for pelvic endometriosis, in particular deeply infiltrating endometriosis. Hum Reprod 13:1952–1956CrossRefPubMed
27.
Zurück zum Zitat Razzi S, Luisi S, Calonaci F, Altomare A, Bocchi C, Petraglia F (2007) Efficacy of vaginal danazol treatment in women with recurrence deeply infiltrating endometriosis. Fertil Steril 88:789–794CrossRefPubMed Razzi S, Luisi S, Calonaci F, Altomare A, Bocchi C, Petraglia F (2007) Efficacy of vaginal danazol treatment in women with recurrence deeply infiltrating endometriosis. Fertil Steril 88:789–794CrossRefPubMed
28.
Zurück zum Zitat Okamura Y, Suzuki J, Honda R, Hoba T, Katabuchi H, Okamura O (2008) Clinical outcome of vaginal danazol suppository use in women with pelvic endometriosis. Fertil Steril 90(Suppl1):S486CrossRef Okamura Y, Suzuki J, Honda R, Hoba T, Katabuchi H, Okamura O (2008) Clinical outcome of vaginal danazol suppository use in women with pelvic endometriosis. Fertil Steril 90(Suppl1):S486CrossRef
30.
Zurück zum Zitat Ferrero S, Tramalloni D, Venturini PL, Remorgida V (2011) Vaginal danazol for women with rectovaginal endometriosis and pain symptoms persisting after insertion of a levonorgestrel-releasing uterine device. Int J Gynaecol Obstet 113:116–119. doi:10.1016/j.ijgo.2010.11.015 CrossRefPubMed Ferrero S, Tramalloni D, Venturini PL, Remorgida V (2011) Vaginal danazol for women with rectovaginal endometriosis and pain symptoms persisting after insertion of a levonorgestrel-releasing uterine device. Int J Gynaecol Obstet 113:116–119. doi:10.​1016/​j.​ijgo.​2010.​11.​015 CrossRefPubMed
31.
Zurück zum Zitat Leone Roberti Maggiore U, Remorgida V, Scala C, Tafi E, Venturini PL, Ferrero S (2014) Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study. Acta Obstet Gynecol Scand 93:239–247. doi:10.1111/aogs.12326 CrossRefPubMed Leone Roberti Maggiore U, Remorgida V, Scala C, Tafi E, Venturini PL, Ferrero S (2014) Desogestrel-only contraceptive pill versus sequential contraceptive vaginal ring in the treatment of rectovaginal endometriosis infiltrating the rectum: a prospective open-label comparative study. Acta Obstet Gynecol Scand 93:239–247. doi:10.​1111/​aogs.​12326 CrossRefPubMed
32.
Zurück zum Zitat Spooner JB (1977) Classification of side-effects to danazol therapy. J Int Med Res 5(Suppl 3):15–17PubMed Spooner JB (1977) Classification of side-effects to danazol therapy. J Int Med Res 5(Suppl 3):15–17PubMed
33.
Zurück zum Zitat Henzl MR, Kwei L (1990) Efficacy and safety of nafarelin in the treatment of endometriosis. Am J Obstet Gynecol 162:570–574CrossRefPubMed Henzl MR, Kwei L (1990) Efficacy and safety of nafarelin in the treatment of endometriosis. Am J Obstet Gynecol 162:570–574CrossRefPubMed
34.
Zurück zum Zitat Godin R, Marcoux V (2015) Vaginally administered danazol: an overlooked option in the treatment of rectovaginal endometriosis? J Obstet Gynaecol Can 37:1098–1103CrossRefPubMed Godin R, Marcoux V (2015) Vaginally administered danazol: an overlooked option in the treatment of rectovaginal endometriosis? J Obstet Gynaecol Can 37:1098–1103CrossRefPubMed
35.
Zurück zum Zitat Brunskill PJ (1992) The effects of fetal exposure to danazol. Br J Obstet Gynaecol 99:212–215CrossRefPubMed Brunskill PJ (1992) The effects of fetal exposure to danazol. Br J Obstet Gynaecol 99:212–215CrossRefPubMed
36.
Zurück zum Zitat Mizutani T, Nishiyama S, Amakawa I, Watanabe A, Nakamuro K, Terada N (1995) Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of a danazol suppository. Fertil Steril 63:1184–1189CrossRefPubMed Mizutani T, Nishiyama S, Amakawa I, Watanabe A, Nakamuro K, Terada N (1995) Danazol concentrations in ovary, uterus, and serum and their effect on the hypothalamic-pituitary-ovarian axis during vaginal administration of a danazol suppository. Fertil Steril 63:1184–1189CrossRefPubMed
37.
Zurück zum Zitat Rotgeri A, Korolainen H, Sundholm O, Schmitz H, Fuhrmann U, Prelle K, Sacher F (2015) Characterization of anastrozole effects, delivered by an intravaginal ring in cynomolgus monkeys. Hum Reprod 30:308–314. doi:10.1093/humrep/deu315 CrossRefPubMed Rotgeri A, Korolainen H, Sundholm O, Schmitz H, Fuhrmann U, Prelle K, Sacher F (2015) Characterization of anastrozole effects, delivered by an intravaginal ring in cynomolgus monkeys. Hum Reprod 30:308–314. doi:10.​1093/​humrep/​deu315 CrossRefPubMed
38.
Zurück zum Zitat Reinecke I, Schultze-Mosgau MH, Nave R, Schmitz H, Ploeger BA (2017) Model-based dose selection for intravaginal ring formulations releasing anastrozole and levonorgestrel intended for the treatment of endometriosis symptoms. J Clin Pharmacol 57:640–651. doi:10.1002/jcph.846 CrossRefPubMed Reinecke I, Schultze-Mosgau MH, Nave R, Schmitz H, Ploeger BA (2017) Model-based dose selection for intravaginal ring formulations releasing anastrozole and levonorgestrel intended for the treatment of endometriosis symptoms. J Clin Pharmacol 57:640–651. doi:10.​1002/​jcph.​846 CrossRefPubMed
39.
Zurück zum Zitat Schultze-Mosgau MH, Waellnitz K, Nave R, Klein S, Kraetzschmar J, Rautenberg T, Schmitz H, Rohde B (2016) Pharmacokinetics, pharmacodynamics, safety and tolerability of an intravaginal ring releasing anastrozole and levonorgestrel in healthy premenopausal women: a phase 1 randomized controlled trial. Hum Reprod 31:1713–1722. doi:10.1093/humrep/dew145 CrossRefPubMed Schultze-Mosgau MH, Waellnitz K, Nave R, Klein S, Kraetzschmar J, Rautenberg T, Schmitz H, Rohde B (2016) Pharmacokinetics, pharmacodynamics, safety and tolerability of an intravaginal ring releasing anastrozole and levonorgestrel in healthy premenopausal women: a phase 1 randomized controlled trial. Hum Reprod 31:1713–1722. doi:10.​1093/​humrep/​dew145 CrossRefPubMed
40.
Zurück zum Zitat Rowland M, Tozer TN (1995) Elimination. Clinical pharmacokinetics: concepts and applications, 3rd edn. Williams and Wilkins, Baltimore, pp 156–183 Rowland M, Tozer TN (1995) Elimination. Clinical pharmacokinetics: concepts and applications, 3rd edn. Williams and Wilkins, Baltimore, pp 156–183
41.
Zurück zum Zitat Dezarnaulds G, Fraser IS (2003) Vaginal ring delivery of hormone replacement therapy—a review. Expert Opin Pharmacother 4:201–212CrossRefPubMed Dezarnaulds G, Fraser IS (2003) Vaginal ring delivery of hormone replacement therapy—a review. Expert Opin Pharmacother 4:201–212CrossRefPubMed
42.
Zurück zum Zitat Nappi RE, Liekens G, Brandenburg U (2006) Attitudes, perceptions and knowledge about the vagina: the International Vagina Dialogue Survey. Contraception 73:493–500CrossRefPubMed Nappi RE, Liekens G, Brandenburg U (2006) Attitudes, perceptions and knowledge about the vagina: the International Vagina Dialogue Survey. Contraception 73:493–500CrossRefPubMed
43.
Zurück zum Zitat Dieben TO, Roumen FJ, Apter D (2002) Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 100:585–593PubMed Dieben TO, Roumen FJ, Apter D (2002) Efficacy, cycle control, and user acceptability of a novel combined contraceptive vaginal ring. Obstet Gynecol 100:585–593PubMed
44.
Zurück zum Zitat Oddsson K, Leifels-Fischer B, de Melo NR, Wiel-Masson D, Benedetto C, Verhoeven CH, Dieben TO (2005) Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception 71:176–182CrossRefPubMed Oddsson K, Leifels-Fischer B, de Melo NR, Wiel-Masson D, Benedetto C, Verhoeven CH, Dieben TO (2005) Efficacy and safety of a contraceptive vaginal ring (NuvaRing) compared with a combined oral contraceptive: a 1-year randomized trial. Contraception 71:176–182CrossRefPubMed
45.
Zurück zum Zitat Fine PM, Tryggestad J, Meyers NJ, Sangi-Haghpeykar H (2007) Safety and acceptability with the use of a contraceptive vaginal ring after surgical or medical abortion. Contraception 75:367–371CrossRefPubMed Fine PM, Tryggestad J, Meyers NJ, Sangi-Haghpeykar H (2007) Safety and acceptability with the use of a contraceptive vaginal ring after surgical or medical abortion. Contraception 75:367–371CrossRefPubMed
46.
Zurück zum Zitat Archer D, Raine T, Darney P, Alexander NJ (2002) An open-label noncomparative study to evaluate the vagina and cervix of NuvaRing® users. Fertil Steril 78:S25CrossRef Archer D, Raine T, Darney P, Alexander NJ (2002) An open-label noncomparative study to evaluate the vagina and cervix of NuvaRing® users. Fertil Steril 78:S25CrossRef
47.
Zurück zum Zitat Roumen FJ, Apter D, Mulders TM, Dieben TO (2001) Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 16:469–475CrossRefPubMed Roumen FJ, Apter D, Mulders TM, Dieben TO (2001) Efficacy, tolerability and acceptability of a novel contraceptive vaginal ring releasing etonogestrel and ethinyl oestradiol. Hum Reprod 16:469–475CrossRefPubMed
48.
Zurück zum Zitat Novák A, de la Loge C, Abetz L, van der Meulen EA (2003) The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability. Contraception 67:187–194CrossRefPubMed Novák A, de la Loge C, Abetz L, van der Meulen EA (2003) The combined contraceptive vaginal ring, NuvaRing: an international study of user acceptability. Contraception 67:187–194CrossRefPubMed
49.
Zurück zum Zitat Ingerslev M (1977) Danazol: an antigonadotrophic agent in the treatment of recurrent pelvic and intestinal endometriosis. Acta Obstet Gynecol Scand 56:343–346CrossRefPubMed Ingerslev M (1977) Danazol: an antigonadotrophic agent in the treatment of recurrent pelvic and intestinal endometriosis. Acta Obstet Gynecol Scand 56:343–346CrossRefPubMed
50.
Zurück zum Zitat Telimaa S, Puolakka J, Rönnberg L, Kauppila A (1987) Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol 1:13–23CrossRefPubMed Telimaa S, Puolakka J, Rönnberg L, Kauppila A (1987) Placebo-controlled comparison of danazol and high-dose medroxyprogesterone acetate in the treatment of endometriosis. Gynecol Endocrinol 1:13–23CrossRefPubMed
51.
Zurück zum Zitat Henzl MR, Corson SL, Moghissi L, Buttram VC, Berqvist C, Jacobson J (1988) Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial. N Engl J Med 318:485–489CrossRefPubMed Henzl MR, Corson SL, Moghissi L, Buttram VC, Berqvist C, Jacobson J (1988) Administration of nasal nafarelin as compared with oral danazol for endometriosis. A multicenter double-blind comparative clinical trial. N Engl J Med 318:485–489CrossRefPubMed
52.
Zurück zum Zitat Burry KA, Patton PE, Illingworth DR (1989) Metabolic changes during medical treatment of endometriosis: nafarelin acetate versus danazol. Am J Obstet Gynecol 160:1454–1459CrossRefPubMed Burry KA, Patton PE, Illingworth DR (1989) Metabolic changes during medical treatment of endometriosis: nafarelin acetate versus danazol. Am J Obstet Gynecol 160:1454–1459CrossRefPubMed
53.
Zurück zum Zitat Fedele L, Arcaini L, Bianchi S, Baglioni A, Vercellini P (1989) Comparison of cyproterone acetate and danazol in the treatment of pelvic pain associated with endometriosis. Obstet Gynecol 73:1000–1004PubMed Fedele L, Arcaini L, Bianchi S, Baglioni A, Vercellini P (1989) Comparison of cyproterone acetate and danazol in the treatment of pelvic pain associated with endometriosis. Obstet Gynecol 73:1000–1004PubMed
54.
Zurück zum Zitat Fedele L, Bianchi S, Viezzoli T, Arcaini L, Candiani GB (1989) Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril 51:781–785CrossRefPubMed Fedele L, Bianchi S, Viezzoli T, Arcaini L, Candiani GB (1989) Gestrinone versus danazol in the treatment of endometriosis. Fertil Steril 51:781–785CrossRefPubMed
55.
Zurück zum Zitat Fraser IS, Shearman RP, Jansen RP, Sutherland PD (1991) A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol. Aust N Z J Obstet Gynecol 31:158–163CrossRef Fraser IS, Shearman RP, Jansen RP, Sutherland PD (1991) A comparative treatment trial of endometriosis using the gonadotrophin-releasing hormone agonist, nafarelin, and the synthetic steroid, danazol. Aust N Z J Obstet Gynecol 31:158–163CrossRef
56.
Zurück zum Zitat The Nafarelin European Endometriosis Trial Group (NEET) (1992) Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. Fertil Steril 57:514–522CrossRef The Nafarelin European Endometriosis Trial Group (NEET) (1992) Nafarelin for endometriosis: a large-scale, danazol-controlled trial of efficacy and safety, with 1-year follow-up. Fertil Steril 57:514–522CrossRef
57.
Zurück zum Zitat Shaw RV (1992) An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team. Fertil Steril 58:265–272CrossRefPubMed Shaw RV (1992) An open randomized comparative study of the effect of goserelin depot and danazol in the treatment of endometriosis. Zoladex Endometriosis Study Team. Fertil Steril 58:265–272CrossRefPubMed
58.
Zurück zum Zitat Vercellini P, Trespidi L, Panazza S, Bramante T, Mauro F, Crosignani PG (1994) Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study. Fertil Steril 62:1136–1142CrossRefPubMed Vercellini P, Trespidi L, Panazza S, Bramante T, Mauro F, Crosignani PG (1994) Very low dose danazol for relief of endometriosis-associated pelvic pain: a pilot study. Fertil Steril 62:1136–1142CrossRefPubMed
59.
Zurück zum Zitat Bromham DR, Booker MW, Rose GL, Wardle PG, Newton JR (1995) Updating the clinical experience in endometriosis—the European perspective. Br J Obstet Gynaecol 102(Suppl 12):12–16CrossRefPubMed Bromham DR, Booker MW, Rose GL, Wardle PG, Newton JR (1995) Updating the clinical experience in endometriosis—the European perspective. Br J Obstet Gynaecol 102(Suppl 12):12–16CrossRefPubMed
60.
Zurück zum Zitat Rotondi M, Labriola D, Rotondi M, Ammaturo FP, Amato G et al (2002) Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis. Eur J Gynaecol Oncol 23:523–526PubMed Rotondi M, Labriola D, Rotondi M, Ammaturo FP, Amato G et al (2002) Depot leuprorelin acetate versus danazol in the treatment of infertile women with symptomatic endometriosis. Eur J Gynaecol Oncol 23:523–526PubMed
61.
Zurück zum Zitat Wong AY, Tang L (2004) An open and randomized study comparing the efficacy of standard danazol and modified triptorelin regimens for postoperative disease management of moderate to severe endometriosis. Fertil Steril 81:1522–1527CrossRefPubMed Wong AY, Tang L (2004) An open and randomized study comparing the efficacy of standard danazol and modified triptorelin regimens for postoperative disease management of moderate to severe endometriosis. Fertil Steril 81:1522–1527CrossRefPubMed
62.
Zurück zum Zitat Kitawaki J, Ishihara H, Kiyomizu M, Honjo H (2008) Maintenance therapy involving a tapering dose of danazol or mid/low doses of oral contraceptive after gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Fertil Steril 89:1831–1835. doi:10.1016/j.fertnstert.2007.05.052 CrossRefPubMed Kitawaki J, Ishihara H, Kiyomizu M, Honjo H (2008) Maintenance therapy involving a tapering dose of danazol or mid/low doses of oral contraceptive after gonadotropin-releasing hormone agonist treatment for endometriosis-associated pelvic pain. Fertil Steril 89:1831–1835. doi:10.​1016/​j.​fertnstert.​2007.​05.​052 CrossRefPubMed
64.
Zurück zum Zitat Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE (2004) Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 81:290–296CrossRefPubMed Ailawadi RK, Jobanputra S, Kataria M, Gurates B, Bulun SE (2004) Treatment of endometriosis and chronic pelvic pain with letrozole and norethindrone acetate: a pilot study. Fertil Steril 81:290–296CrossRefPubMed
65.
Zurück zum Zitat Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T (2004) The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 19:160–167CrossRefPubMed Soysal S, Soysal ME, Ozer S, Gul N, Gezgin T (2004) The effects of post-surgical administration of goserelin plus anastrozole compared to goserelin alone in patients with severe endometriosis: a prospective randomized trial. Hum Reprod 19:160–167CrossRefPubMed
66.
Zurück zum Zitat Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE (2005) Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril 84:300–304CrossRefPubMed Amsterdam LL, Gentry W, Jobanputra S, Wolf M, Rubin SD, Bulun SE (2005) Anastrazole and oral contraceptives: a novel treatment for endometriosis. Fertil Steril 84:300–304CrossRefPubMed
67.
Zurück zum Zitat Remorgida V, Abbamonte LH, Ragni N, Fulcheri E, Ferrero S (2007) Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV endometriosis. Aust N Z J Obstet Gynaecol 47:222–225CrossRefPubMed Remorgida V, Abbamonte LH, Ragni N, Fulcheri E, Ferrero S (2007) Letrozole and desogestrel-only contraceptive pill for the treatment of stage IV endometriosis. Aust N Z J Obstet Gynaecol 47:222–225CrossRefPubMed
68.
Zurück zum Zitat Remorgida V, Abbamonte HL, Ragni N, Fulcheri E, Ferrero S (2007) Letrozole and norethisterone acetate in rectovaginal endometriosis. Fertil Steril 88:724–726CrossRefPubMed Remorgida V, Abbamonte HL, Ragni N, Fulcheri E, Ferrero S (2007) Letrozole and norethisterone acetate in rectovaginal endometriosis. Fertil Steril 88:724–726CrossRefPubMed
69.
Zurück zum Zitat Ferrero S, Camerini G, Seracchioli R, Ragni N, Venturini PL, Remorgida V (2009) Letrozole combined with norethisterone acetate compared with norethisterone acetate alone in the treatment of pain symptoms caused by endometriosis. Hum Reprod 24:3033–3041. doi:10.1093/humrep/dep302 CrossRefPubMed Ferrero S, Camerini G, Seracchioli R, Ragni N, Venturini PL, Remorgida V (2009) Letrozole combined with norethisterone acetate compared with norethisterone acetate alone in the treatment of pain symptoms caused by endometriosis. Hum Reprod 24:3033–3041. doi:10.​1093/​humrep/​dep302 CrossRefPubMed
70.
Zurück zum Zitat Roghaei MA, Tehrany HG, Taherian A, Koleini N (2010) Effects of letrozole compared with danazol on patients with confirmed endometriosis: a randomized clinical trial. Int J Fertil Steril 4:67–72 Roghaei MA, Tehrany HG, Taherian A, Koleini N (2010) Effects of letrozole compared with danazol on patients with confirmed endometriosis: a randomized clinical trial. Int J Fertil Steril 4:67–72
73.
Zurück zum Zitat Ferrero S, Venturini PL, Gillott DJ, Remorgida V (2011) Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial. Reprod Biol Endocrinol 9:88. doi:10.1186/1477-7827-9-88 CrossRefPubMedPubMedCentral Ferrero S, Venturini PL, Gillott DJ, Remorgida V (2011) Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial. Reprod Biol Endocrinol 9:88. doi:10.​1186/​1477-7827-9-88 CrossRefPubMedPubMedCentral
74.
Zurück zum Zitat Sa Alborzi, Hamedi B, Omidvar A, Dehbashi S, So Alborzi, Alborzi M (2011) A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis. Arch Gynecol Obstet 284:105–110. doi:10.1007/s00404-010-1599-6 CrossRefPubMed Sa Alborzi, Hamedi B, Omidvar A, Dehbashi S, So Alborzi, Alborzi M (2011) A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis. Arch Gynecol Obstet 284:105–110. doi:10.​1007/​s00404-010-1599-6 CrossRefPubMed
Metadaten
Titel
“Per vaginam” topical use of hormonal drugs in women with symptomatic deep endometriosis: a narrative literature review
verfasst von
Laura Buggio
Caterina Lazzari
Ermelinda Monti
Giussy Barbara
Nicola Berlanda
Paolo Vercellini
Publikationsdatum
29.06.2017
Verlag
Springer Berlin Heidelberg
Erschienen in
Archives of Gynecology and Obstetrics / Ausgabe 3/2017
Print ISSN: 0932-0067
Elektronische ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-017-4448-z

Weitere Artikel der Ausgabe 3/2017

Archives of Gynecology and Obstetrics 3/2017 Zur Ausgabe

Update Gynäkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert – ganz bequem per eMail.