Dienogest in women with persistent endometriosis-related pelvic pain during norethisterone acetate treatment

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Abstract

Objective

To evaluate patient satisfaction at 6-months dienogest (DNG) treatment in women with symptomatic rectovaginal endometriosis who had pain persistence and were unsatisfied after 6-months of norethisterone acetate (NETA) therapy.

Study design

This 24-weeks pilot open-label prospective study enrolled 25 women. The main outcome was the degree of patient satisfaction measured by using a Likert scale. Secondary outcomes were to evaluate differences in endometriosis-related pain, quality of life, sexual function changes and volumetric nodules changes during DNG compared to NETA treatment.

Results

Patient satisfaction improved at 3- and 6-months (p < 0.001, respectively) treatment with DNG compared with baseline treatment with NETA. Six months DNG treatment decreased the intensity of all the endometriosis-associated pain (chronic pelvic pain, dyspareunia, dyschezia) compared to baseline (p < 0.001 for all comparisons). Quality of life and quality of sexual life evaluated with the EHP-30 and FSFI, respectively, increased after 6 months treatment. The volume of the endometriotic nodules did not significantly change during treatment.

Conclusions

This study confirms the efficacy of DNG in treating symptomatic women with rectovaginal endometriosis even in a particular endometriotic subpopulation of NETA “resistant” patients. Further randomized clinical trials comparing these two progestins both in first than second line are warranted.

Introduction

Rectovaginal endometriosis is one of the more common pelvic localizations of this disease and it usually causes pain symptoms including dysmenorrhea, chronic pelvic pain, dyschezia and deep dyspareunia. When pregnancy is not desired, hormonal therapies may be administered to symptomatic patients who decline surgery or to patients who previously underwent incomplete excision of deep endometriotic lesions and wish to avoid further surgery [1].

Current medical therapies (including progestins) do not eradicate endometriotic lesions but they are efficacious and safe in relieving pain symptoms associated with rectovaginal endometriosis [2].

Several progestins have been demonstrated to be safe end efficacious in controlling endometriosis associated pain-symptoms and they can be recommended as first-line therapy in this setting [3], [4]. Amongst progestins, norethisterone acetate is one of the most commonly used medical treatment for pelvic endometriosis and it was demonstrated to be safe and efficacious in relieving pain symptoms [5], [6], [7], [8], [9]. However, a percentage of patients ranging from 20% to 37% is dissatisfied after 6-months NETA treatment in different studies, suggesting that NETA is not efficacious or not well tolerated in around one over 3 patients treated [6], [7], [8], [9].

In the last years several research efforts has been focused on DNG, an oral derivative of 19-nortestosterone, specifically designed for the treatment of endometriosis. This compound slightly differs from other progestins for the presence of a cyanometilic group in place of an ethinyl group in position 17alpha, thus combining the advantages of nortestosterone derivatives with the benefits of progesterone derivatives [10]. DNG has been shown to be effective in reducing pain symptoms associated with endometriosis thus representing an important option in the medical treatment of this disease [11], [12], [13], [14], [15], [16], [17], [18], [19]. Its pharmacological mechanism slightly differs from other progestins; it appears to involve not only PR activation but also regulation of PR subtypes [10], suggesting a possible role of DNG in patient unsatisfied/resistant to NETA treatment. Given this background we planned a 24-week prospective open-label study evaluating the efficacy and tolerability of DNG in women with rectovaginal endometriosis who were unsatisfied with previous 6-months NETA treatment.

Section snippets

Study population

This 6-months prospective, open-label trial was performed in an academic centre for the diagnosis and treatment of endometriosis.

Criteria for inclusion in the study were: patients treated with NETA (2.5–5 mg/day, Primolut-Nor®; Schering, formerly NV Organon, Oss, the Netherlands) for 6 months who had pain persistence (at least one symptom with intensity >8 on a visual analogue scale) and were unsatisfied (Likert scale of 4) or very unsatisfied (Likert scale of 5) with the treatment. Patients had

Results

Out of thirty-six patients fitting the inclusion criteria during the study period, six were excluded for incomplete diaries during the NETA treatment (6/36, 16.7%). Five patients did not accept the treatment (5/30, 16.7%) and one patient was lost to follow-up, thus 25 patients were evaluable for the intention-to-treat analysis (ITT). The demographic characteristics and baseline data of the patients included in the study are presented in Table 1.

At the 6-month assessment in the ITT analysis, 3

Comments

In this 24-week, open-label prospective study, DNG 2 mg daily orally was associated with increased patient satisfaction, quality of sexual life and significant reductions in pain symptoms in patients with rectovaginal endometriosis who were unsatisfied with previous 6 months treatment with NETA.

The improvement in endometriosis-associated pain with DNG was accompanied by an acceptable safety and tolerability profile in term of clinical and biochemical features, consistent with observations in

Conflict of interest

None.

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