Therapeutics · Hormonal Agents

Intravaginal progesterone as a fertility-sparing treatment for symptomatic adenomyosis: preliminary results from a monocentric study

De Cicco Nardone C, Sangiovanni MC, Sangiovanni GM, Plotti F, Montera R, Luvero D, Angioli R, Terranova C

Published April 28, 2026 Archives of gynecology and obstetrics, 313(1)
DOI 10.1007/s00404-026-08361-y PMID 42050103 PMC PMC13124872

RRM Academy Synopsis

Adenomyosis symptom scores fell on vaginal progesterone in 65 women

Symptom scores for adenomyosis fell over 6 months in 65 women using vaginal progesterone, in a one-hospital study with no comparison group. The women wanted to keep their fertility. They scored pain, bleeding and painful sex from 0 to 10.

Key Findings

  • Median dysmenorrhea (painful periods) score fell from 9 to 6 (p < 0.001) at 6 months among the 65 women who completed follow-up.
  • Median abnormal uterine bleeding score fell from 8 to 6 (p < 0.001) in the same 65 women.
  • Among the 40 women who completed those questionnaires, median chronic pelvic pain fell from 5.5 to 3.5 (p < 0.001) and dyspareunia (painful sex) from 2 to 0 (p = 0.020).
  • Women gave the treatment a mean satisfaction score of 7.5 out of 10 for its effect on quality of life at 6 months.
  • Of 85 women enrolled, 65 completed the study. Four of the 20 who did not finish became pregnant during treatment.

Interpretation

This is a prospective observational study at one Rome hospital, with no comparison group. Every woman received the same treatment, which makes it hard to separate progesterone's effect from a placebo effect. The authors call this a significant limitation. Twenty of 85 women did not finish, and only 40 answered the pelvic pain and painful sex questionnaires. The authors say this attrition could favor the treatment. Symptoms were self-rated, and no sample size calculation was done. The four pregnancies were exploratory, since pregnancy was not an endpoint.

RRM Context

Restorative reproductive medicine looks for what drives symptoms and supports the ovulatory cycle. The authors say some women who want to conceive avoid combined pills, and the levonorgestrel IUD is a contraceptive. Dienogest, which the authors cite, is a synthetic progestin. This study used micronized natural progesterone.

Abstract

Purpose

Adenomyosis is a chronic uterine disorder characterised by ectopic endometrial tissue within the myometrium, frequently associated with dysmenorrhea, abnormal uterine bleeding (AUB), chronic pelvic pain (CPP), and dyspareunia. No standardised guidelines are currently available for its management, and therapeutic options remain limited for women seeking fertility preservation. This study aimed to evaluate the efficacy of intravaginal progesterone in alleviating adenomyosis-related symptoms in patients seeking fertility preservation.

Methods

In this prospective monocentric observational study, 85 patients aged 22-50 years with ultrasound-confirmed symptomatic adenomyosis were enrolled between April 2020 and April 2024. Inclusion criteria were age 18-55 years, BMI 18-35, and a Visual Analogue Scale (VAS) score ≥ 7 for dysmenorrhea, AUB, CPP, or dyspareunia. All patients received 200 mg/day of intravaginal progesterone for 10 days per cycle. Symptom severity was assessed using VAS scores at baseline and at 6 months. Data were analysed using non-parametric statistical tests.

Results

Sixty-five patients completed the 6-month follow-up. Four patients conceived during treatment and were excluded from the final analysis. Statistically significant improvements were observed for all assessed symptoms (all p < 0.05). Median VAS scores decreased for dysmenorrhea (9 to 6, p < 0.001), AUB (8 to 6, p < 0.001), chronic pelvic pain (5.5 to 3.5, p < 0.001), and dyspareunia (2 to 0, p = 0.020). The overall treatment satisfaction was high, with a mean Likert score of 7.5 out of 10.

Conclusion

Intravaginal progesterone appears to be an effective fertility-sparing treatment for symptomatic adenomyosis, providing significant relief across all primary symptoms, with high patient satisfaction. Larger controlled studies are warranted to confirm these preliminary findings and further define its role in clinical practice.

Topics

By this author

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Therapeutics › Hormonal Agents › Progesterone and Progestins · Uterine and Pelvic Conditions › Adenomyosis › Adenomyosis Management · General Gynecology › Pelvic Pain › Chronic Pelvic Pain
Francesco Plotti, Roberto Angioli, Corrado Terranova
F Plotti, R Angioli, C Terranova
PMID 42050103 42050103 DOI 10.1007/s00404-026-08361-y 10.1007/s00404-026-08361-y De Cicco Nardone et al. 2026, De Cicco Nardone 2026