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Treatment of symptomatic rectovaginal endometriosis with an estrogen–progestogen combination versus low-dose norethindrone acetate
Open accessAbstract
Objective To evaluate the efficacy, safety, and tolerability of an estrogen-progestogen combination versus low-dose norethindrone acetate in the treatment of persistent pain after surgery for symptomatic rectovaginal endometriosis.Design Randomized controlled trial.Setting Academic center.Patient(s) Ninety women with recurrent moderate or severe pelvic pain after unsuccessful conservative surgery for symptomatic rectovaginal endometriosis.Intervention(s) Twelve-month, continuous treatment with oral ethinyl E2, 0.01 mg, plus cyproterone acetate, 3 mg/day, or norethindrone acetate, 2.5 mg/day.Main outcome measure(s) Degree of satisfaction with therapy.Result(s) Seven women in the ethinyl E2 plus cyproterone acetate arm and five in the norethindrone acetate arm withdrew because of side effects (n=5), treatment inefficacy (n=6), or loss to follow-up (n=1). At 12 months, dysmenorrhea, deep dyspareunia, nonmenstrual pelvic pain, and dyschezia scores were substantially reduced without major between-group differences. Both regimens induced minor unfavorable variations in the serum lipid profile. According to an intention-to-treat analysis, 28 (62%) out of 45 patients in the ethinyl E2 plus cyproterone acetate group and 33 (73%) out of 45 in the norethindrone acetate group were satisfied with the treatment received.Conclusion(s) Low-dose norethindrone acetate could be considered an effective, tolerable, and inexpensive first-choice medical alternative to repeat surgery for treating symptomatic rectovaginal endometriotic lesions in patients who do not seek conception.
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In the citing paper
“Low-dose NETA 2.5 mg/day orally is considered an effective, tolerable and inexpensive first choice for symptomatic rectovaginal endometriosis, significantly decreasing VAS scores for dysmenorrhea and dyspareunia [209].”
From Hormonal treatments for endometriosis: The endocrine background (2022) · cites this paper as [209]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Reported response rates for therapy with 2.5 mg norethindrone acetate per day in endometriosis-associated pain range between 74 and 92%.”
From Pain and functional outcomes after surgical versus hormonal treatment in rectovaginal endometriosis: a retrospective cohort study (2026) · cites this paper as [29]
The cited source says what the claim attributes to it.
In the citing paper
“Evidence for hormonal treatment specifically in RVE is less abundant and only one randomised-controlled trial was identified in the literature [29].”
From Pain and functional outcomes after surgical versus hormonal treatment in rectovaginal endometriosis: a retrospective cohort study (2026) · cites this paper as [29]
In the citing paper
“Based on our previous experience, the proportion of endometriosis patients satisfied with OC treatment is $65% (20,57).”
From A stepped-care approach to symptomatic endometriosis management: A participatory research initiative (2018) · cites this paper as [20]
In the citing paper
“Both treatments were equally effective in the management of pain symptoms and on the reduction of lesion size at ultrasound.”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [13]
In the citing paper
“Overall, 73% women in the NETA group were satisfied or very satisfied with treatment compared to 62% in the EP group.”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [13]
In the citing paper
“The lower dosage increases the tolerability, reducing weight gain and androgenic side effects, and limits the negative impact on serum cholesterol values [13].”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [13]
In the citing paper
“numerous studies by independent groups demonstrated the efficacy of a reduced daily dose of 2.5 mg [13-16].”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [13]
In the citing paper
“in Italy, the monthly cost of treatment with 2.5 mg/d is less than 2 US $ [13].”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [13]
In the citing paper
“whereas low-dose oral NETA is probably the best choice for rectovaginal lesions”
From “Waiting for Godot”: a commonsense approach to the medical treatment of endometriosis (2011) · cites this paper as Vercellini et al., 2005
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Metadata
- Authors
- Vercellini, P., Pietropaolo, G., De Giorgi, O., Pasin, R., Chiodini, A., & Crosignani, P. G.
- Affiliations
- University of Milan (IT)
- Corresponding author
- Vercellini, Paolo
- ORCID
- Vercellini, Paolo
- Venue
- Fertility and Sterility
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 84
- Issue
- 5
- Pages
- 1375-1387
- ISSN
- 0015-0282 (ISSN-L)
- OpenAlex
- W2062896185
- Cited by
- 197
- References
- 28
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 8 · 2020: 13 · 2019: 6 · 2018: 18 · 2017: 13 · 2016: 9 · 2015: 13 · 2014: 14 · 2013: 9 · 2012: 15
- FWCI
- 6.68
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Fertility and Sterility (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Obstetrics and Gynecology › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Obstetrics and Gynecology › Gynecological conditions and treatments
- Keywords
- rectovaginal endometriosis, norethindrone acetate, ethinyl estradiol, cyproterone acetate, dysmenorrhea, dyspareunia, dyschezia, treatment satisfaction, lipid profile
- MeSH terms
- Norethindrone Acetate, Adolescent, Adult, Drug Therapy, Combination, Endometriosis, Estrogens, Female, Humans, Middle Aged, Norethindrone, Pain Measurement, Progestins, Rectal Diseases, Vaginal Diseases, Estrogen Replacement Therapy, Confidence Intervals, Statistics, Nonparametric
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