Skip to main content


Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Nomegestrol acetate versus combined oral contraceptive as rapid endometrial preparation for operative hysteroscopy: a prospective randomised pilot study


Hysteroscopy is now the established “gold standard” for the assessment and treatment of intrauterine pathology such as fibroids, polyps, synechiae, septa and endometrial resection and/or destruction, and is regarded as a safe, acceptable and well-tolerated procedure [15]. In fertile women, hysteroscopic procedures are best performed when the endometrium is thin because the operating time is lessened and fluid absorption decreases, making surgery easier [69]. For these reasons, the days immediately after menstruation are the best period for hysteroscopy. Scheduling surgery during the early follicular phase is not always possible, so several drugs have been proposed to reduce endometrial thickness, intra-operative bleeding, surgical difficulties and duration of surgery [6, 10, 11]. Even if preoperative treatment with gonadotropin-releasing hormone analogues (GnRH-a) or danazol for 2 or 3 months has been recommended to remove large intramural sub-mucous myomas or perform endometrial resection [9], they are not as often used for procedure preparation especially in case of minor hysteroscopy. GnRH-a result in a state of temporary menopause and are expensive, while danazol induces unfavourable side effects including weight gain, growth of hair, acne and general malaise [12]. Several studies have reported that gestrinone also is capable of reducing uterine volume, menorrhagia and endometrial thickness [1315].

A limiting factor existing among the previous treatments is the long time required to reduce the endometrium. Recently, to speed up endometrial preparation, other original treatments have been proposed as oral progestins and vaginal raloxifen [16], nomegestrol acetate [17] and oral contraceptives [18], and they obtained good results in terms of preparation of the endometrium, cost and acceptability. Shortening the preparation time before surgery may improve patient compliance and work organization [19].

The aim of this prospective, randomised study was to compare the effectiveness of nomegestrol acetate versus combined oral contraceptive treatments as short preoperative endometrial preparation before hysteroscopic surgery.

Materials and methods

Between February and July 2011, 42 pre-menopausal women were prospectively enrolled in the study. The inclusion criteria were: hysteroscopic diagnosis of endocavitary pathologies and regular menstrual cycle rhythms for the previous 6 months. Exclusion criteria were: age <18 and >45, hormonal therapies in the previous 12 weeks, previous uterine surgery, concomitant adnexal pathologies, endometriosis and cardiovascular, hepatic or renal impairment.

The study protocol was conformed to the ethical guidelines of the 1975 Helsinki Declaration, and the Institutional Review Board of the department approved it. Written informed consent was obtained from each female patient upon enrolment.

Before treatment (day 14 of the menstrual cycle), each woman received a trans-vaginal ultrasound (TVUS) evaluation to measure endometrial thickness, ovarian size and number of ovarian follicles. On day 1 of the menstrual cycle, patients were randomised to receive 3 weeks of therapy with 5 mg of nomegestrol acetate daily (group A, n = 21) or 20 μg of ethinyl estradiol/75 mg gestodene daily (group B, n = 21). Allocation to one of the two parallel treatment groups (21 in each) was performed using the SPSS v 17.0 randomisation program (SPSS Inc., Chicago, IL). Both surgeons were not aware of the therapy at the time of surgery.

Surgery was performed the day after the last assumption of hormonal medicament. Patients were hospitalized the same day of surgery. Preoperative exams as TVUS, ECG and routine blood test were performed in the early morning, and side effects experienced by the patients during treatment were recorded. The effectiveness of the therapy was intraoperatively evaluated by assessing the visibility of the uterine cavity, the endometrial features, the difficulty of the procedure and the success of surgery. Hormonal effects of the studied drugs are evaluated by assessing endometrial thickness and number and size of ovarian follicles.

Operative hysteroscopy was performed under general anaesthesia by two expert endoscopic surgeons (L.M. and L.M.), using a bipolar resectoscope. More specifically, after the tenaculum was placed and the cervix dilated to Hegar 8, the procedure used a 22-Fr continuous-flow resectoscope fitted with a cutting loop electrode at a power setting of 120-W cutting current. A sterile saline solution was used for uterine distension.

To evaluate the visibility, we assigned a score from 0 to 1 for each of the five following parameters: left ostium, right ostium, fundus, anterior wall and posterior wall. A score from 0 to 2 was classified as “bad visibility”, a score of 3 was classified as “moderate visibility” and a score from 4 to 5 was rated as “good visibility”.

The endometrial features assessed by direct vision during hysteroscopic procedure were classified according to Baggish and Barbott as: “atrophic” when the endometrium was thin, regular and pale; “normal” when the endometrial appearance was compatible with the proliferative phase; “normal with small hyperplastic areas” when only small focused areas of thickness were present and “hyperplastic” when a diffuse thick polypoid endometrium was found [6].

The difficulty of the procedure and the success of surgery were evaluated by the surgeon marking two separated 100-mm visual analogue scale from 0 (minimum) to 100 (maximum). One month after surgery, women underwent a diagnostic hysteroscopy to confirm the completeness of the treatment.

Statistical analysis was performed with SPSS 11 (SPSS, Chicago, IL). Data were expressed as mean ± SD (range) or as number (percent) of cases. To compare data between the two groups, a Student's t test was used for parametric data and the Mann–Whitney test for non-parametric data. Dichotomous variables were analysed with the χ 2 test and the Fischer exact test, when appropriate. A P value of <0.05 was considered statistically significant.


Between February to July 2011, we identified 42 pre-menopausal women who were consecutively enrolled in the study. The two study groups were similar for age, parity and body mass index (BMI) (Table 1), as well as for prevalence of uterine endocavitary pathologies (Fig. 1). No differences were retrieved at enrolment between groups in terms of endometrial thickness (group A, 7.2 ± 1.2 mm; group B, 6.9 ± 0.9 mm; P = 0.08) and mean follicular diameter (P = 0.07) (Table 2).

Table 1 Patients' main characteristics
Fig. 1

Prevalence of endocavitary pathologies. NOMAC: 5 mg nomegestrol acetate; EE/EGST: 20 μg ethinyl estradiol/75 mg gestodene

Table 2 Endometrial and follicle pattern before and after treatment

The reduction in endometrial thickness in group B (EE/GSD) was statistically significantly greater than in group A (NOMAC) (P < 0.001) as well as the ovarian dominant follicle mean diameter (P < 0.0001) (Table 2).

An assessment of the endometrium during surgery showed that all patients responded to the treatment with a significant difference between groups. Surgeon satisfaction in terms of endometrial preparation was higher for women of group B compared with group A (83.4 % “good visibility” group B vs 57.5 % group A) (Table 3). At hysteroscopy, the endometrial mucosa appeared to be very thin, hypotrophic, regular and pale in all of the women of the two groups. However, we observed some cases of “hyperplastic endometrial features” in group A; the endometrial surface was high and irregular, with areas of stromal oedema and glandular development (Fig. 2).

Table 3 Visibility score
Fig. 2

Endometrial features during hysterosocopy. NOMAC 5 mg nomegestrol acetate, EE/EGST 20 μg ethinyl estradiol/75 mg gestodene

Difficulty to perform hysteroscopic surgery was greater in group A, mean 5 (range 3–9), than with group B, mean 2 (range 0–6), P < 0.001. No significant differences emerged in relation to time taken for cervical dilatation, operating time, postoperative complications and completeness of surgery.


The success of hysteroscopic surgery is related to good and constant visibility during the procedure, bearing in mind that the surgical field is extremely limited and very often narrowed by endometrial thickness and by the endouterine pathology itself [20]. With a prepared endometrium, the uterine cavity became easier to explore, and endocavitary pathologies are easy to detect and treat. A preoperative pharmacological treatment for endometrial mucosa thinning is recommended to achieve the best conditions of visibility [21, 22]. The efficacy of GnRH agonists and danazol administration for thinning the endometrium before hysteroscopic surgery has been reported by several investigators [9, 12]. However, they are expensive drugs with many side effects, and they require a long time to thin the endometrium.

Oral contraceptives and progestogens have been also proposed as a rapid treatment before hysteroscopic surgery, but only few randomised data are available to assess their effectiveness as endometrial thinning agents [1518].

Shortening the preparation time before surgery may increase patients' compliance and improve work organization. The results of this study demonstrate that a short treatment with both 5 mg of nomegestrol acetate and 20 μg of ethinyl estradiol/75 mg gestodene before operative hysteroscopy provides a very fast and effective endometrial suppression.

According to TVUS evaluation, the endometrial features under direct hysteroscopic exploration of the cavity demonstrated that endometrial preparation was better in group B than in group A. Indeed, all group B women had very thin, pale and regular endometrium. In contrast, in group A in some cases, the endometrial surface was high and irregular, with areas of stromal oedema and glandular development probably related to the progestin-induced decidualization. Accordingly, surgeon satisfaction was significantly greater for group B. Side effects, owing to the short period over which the two drugs were administered, were infrequent in both treatments, without significant differences between the two groups. Limitations of this trial were the limited number of cases and the presupposition that no variation occurs in endometrial features in the natural menstrual cycle; nevertheless, it is unlikely that the natural variations could significantly affect the study results.


In conclusion, our data suggest that both treatments, used for a brief period, are good ways to prepare the endometrium before hysteroscopic surgery. Satisfactory endometrial preparation can be obtained with only 3 weeks of treatment, and this improves acceptability and scheduling for hysteroscopic treatment. However, the endometrial preparation with 5 mg nomegestrol acetate appears to be less comfortable for the surgeon in terms of visibility of the uterine cavity than 20 μg ethinyl estradiol/75 mg gestodene endometrial preparation. No differences in completeness of surgery, operative time and intra-operative complications were noticed.


  1. 1.

    Gimpelson RJ, Whalen TR (1995) Hysteroscopy as gold standard for evaluation of abnormal uterine bleeding. Am J Obstet Gynecol 173:1637–1638

  2. 2.

    Sutton C (2006) Hysteroscopic surgery. Best Pract Res Clin Obstet Gynaecol 20:105–137

  3. 3.

    Bosteels J, Weyers S, Puttemans P, Panayotidis C, Van Herendael B, Gomel V, Mol BW, Mathieu C, D'Hooghe T (2010) The effectiveness of hysteroscopy in improving pregnancy rates in subfertile women without other gynaecological symptoms: a systematic review. Hum Reprod Update 16:1–11

  4. 4.

    Di Spiezio SA, Mazzon I, Bramante S, Bettocchi S, Bifulco G, Guida M, Nappi C (2008) Hysteroscopic myomectomy: a comprehensive review of surgical techniques. Hum Reprod Update 14:101–119

  5. 5.

    Goldstein SR (2009) The role of transvaginal ultrasound or endometrial biopsy in the evaluation of the menopausal endometrium. Am J Obstet Gynecol 201:5–11

  6. 6.

    Rai VS, Gillmer MD, Gray W (2000) Is endometrial pre-treatment of value in improving the outcome of transcervical resection of the endometrium? Hum Reprod 15:1989–1992

  7. 7.

    Römer T, Schmidt T, Foth D (2000) Pre- and postoperative hormonal treatment in patients with hysteroscopic surgery. Contrib Gynecol Obstet 20:1–12

  8. 8.

    Brooks PG, Serden SP, Davos I (1991) Hormonal inhibition of the endometrium for resectoscopic endometrial ablation. Am J Obstet Gynecol 164:1601–1606

  9. 9.

    Parazzini F, Vercellini P, De Giorgi O, Pesole A, Ricci E, Crosignani PG (1998) Efficacy of preoperative medical treatment in facilitating hysteroscopic endometrial resection, myomectomy and metroplasty: literature review. Hum Reprod 13:2592–2597

  10. 10.

    Vercellini P, Perino A, Consonni R, Trespidi L, Parazzini F, Crosignani PG (1996) Treatment with a gonadotrophin releasing hormone agonist before endometrial resection: a multicentre, randomised controlled trial. Br J Obstet Gynaecol 103:562–568

  11. 11.

    Donnez J, Vilos G, Gannon MJ, Stampe-Sorensen S, Klinte I, Miller RM (1997) Goserelin acetate (Zoladex) plus endometrial ablation for dysfunctional uterine bleeding: a large randomized, double-blind study. Fertil Steril 68:29–36

  12. 12.

    Sowter MC, Lethaby A, Singla AA (2002) Pre-operative endometrial thinning agents before endometrial destruction for heavy menstrual bleeding. Cochrane Database Syst 3:CD001124

  13. 13.

    Fedele L, Bianchi S, Gruft L, Bigatti G, Busacca M (1996) Danazol versus a gonadotropin-releasing hormone agonist as preoperative preparation for hysteroscopic metroplasty. Fertil Steril 65:186–188

  14. 14.

    Marchini M, Fedele L, Bianchi S, Di Nola G, Nava S, Vercellini P (1992) Endometrial patterns during therapy with danazol or gestrinone for endometriosis: structural and ultrastructural study. Hum Pathol 23:51–56

  15. 15.

    Triolo O, De Vivo A, Benedetto V, Falcone S, Antico F (2006) Gestrinone versus danazol as preoperative treatment for hysteroscopic surgery: a prospective, randomized evaluation. Fertil Steril 85:1027–1031

  16. 16.

    Cicinelli E, Pinto V, Tinelli R, Saliani N, De Leo V, Cianci A (2007) Rapid endometrial preparation for hysteroscopic surgery with oral desogestrel plus vaginal raloxifene: a prospective, randomized pilot study. Fertil Steril 88:698–701

  17. 17.

    Florio P, Imperatore A, Litta P, Franchini M, Calzolari S, Angioni S, Gabbanini M, Bruni L, Petraglia F (2010) The use of nomegestrol acetate in rapid preparation of endometrium before operative hysteroscopy in pre-menopausal women. Steroids 12:912–917

  18. 18.

    Grow DR, Iromloo K (2006) Oral contraceptives maintain a very thin endometrium before operative hysteroscopy. Fertil Steril 85:204–207

  19. 19.

    Heinonen PK, Helin R (2009) Endometrial resection following levonorgestrel intrauterine system treatment for menorrhagia. Gynecol Surgery 9:245–249

  20. 20.

    Panayotidis C, Weyers S, Bosteels J, Van Herendael B (2009) Intrauterine adhesions (IUA): has there been progress in understanding and treatment over the last 20 years? Gynecol Surgery 6:197–211

  21. 21.

    Lewis BV (1994) Guidelines for endometrial ablation. British Society of Gynaecological Endoscopy. Br J Obstet Gynaecol 101:470–473

  22. 22.

    Nicolaou D, Salman G, Richardson R (2009) Operative hysteroscopy in the outpatient setting: its role within a gynaecology service. Gynecol Surgery 6:21–24

Download references

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Author information

Correspondence to Liliana Mereu.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Mereu, L., Giunta, G., Carri, G. et al. Nomegestrol acetate versus combined oral contraceptive as rapid endometrial preparation for operative hysteroscopy: a prospective randomised pilot study. Gynecol Surg 9, 401–404 (2012).

Download citation


  • Hysteroscopy
  • Nomegestrol acetate
  • Endometrial preparation
  • Ethinyl estradiol and gestodene oral contraceptive