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Letrozole vs Danazol for Endometriosis-Related Pain: Randomized Trial (LET-DAN RCT)

S

Sidra Salman

Status and phase

Completed
Phase 2

Conditions

Endometriosis

Treatments

Drug: danazol
Drug: Letrozole

Study type

Interventional

Funder types

Other

Identifiers

NCT07183787
SMDC/SMRC/79-18

Details and patient eligibility

About

Background:

Endometriosis is a chronic gynecological condition defined by the ectopic presence of endometrial glands and stroma outside the uterine cavity, most commonly diagnosed via laparoscopy. While its exact etiology remains uncertain, a positive family history is considered a significant risk factor. Danazol has historically demonstrated efficacy in alleviating endometriosis-related pain, while letrozole, primarily used in neoadjuvant settings, has recently emerged as a promising alternative. This study aimed to compare the mean reduction in pain scores between letrozole and danazol in women with laparoscopically confirmed endometriosis.

Objective:

To compare the efficacy of letrozole versus danazol in reducing pain scores among women diagnosed with endometriosis.

Material & Methods:

Study Design: Randomized control trial Setting: Department of Obstetrics & Gynaecology, Sharif Medical and Dental Hospital

Full description

Introduction:

Endometriosis is defined by the ectopic presence of functional endometrial glands and stroma outside the uterine cavity, most commonly diagnosed via direct laparoscopic visualization (1). Clinical manifestations include dysmenorrhea, dyspareunia, chronic pelvic pain, and infertility-each of which may significantly impair a woman's quality of life (2). It is a chronic, estrogen-dependent inflammatory condition predominantly affecting women of reproductive age, though adolescents may also be affected (3). Its true prevalence remains uncertain due to underdiagnosis and a diagnostic delay averaging nearly a decade, often attributed to normalization of symptoms and missed recognition by primary care providers. Beyond physical symptoms, endometriosis exerts a profound psychosocial and economic burden on affected individuals, their families, and healthcare systems globally (4).

Pathophysiology and Clinical Impact of Ectopic Endometrial Tissue in Endometriosis Ectopic endometrial tissue typically localizes in the dependent regions of the pelvis, such as the posterior and anterior cul-de-sac, uterosacral ligaments, ovaries, and fallopian tubes; however, extra-pelvic involvement is also possible (5). These implants respond to cyclic hormonal stimulation much like eutopic endometrium, undergoing phases of proliferation, secretion, and subsequent shedding. The metabolic by-products especially cytokines and prostaglandins foster a chronic inflammatory milieu characterized by neovascularization, fibrosis, and pain sensitization. Immunologic dysregulation is also implicated, including aberrant T- and B-cell responses, complement system activation, and elevated interleukin-6 (IL-6) levels in affected individuals. These immunoinflammatory mechanisms lead to adhesion formation, anatomic distortion, and chronic pelvic pain which are the hallmark features of the disease (5).

Classification of Endometriosis:

Endometriosis can be classified into three main types based on lesion location. Superficial peritoneal endometriosis is the most common form, characterized by lesions affecting the peritoneum, the thin membrane lining the pelvic cavity. Endometriomas, or ovarian lesions, are dark, fluid-filled cysts ("chocolate cysts") that develop within the ovaries, often resistant to treatment and capable of damaging healthy ovarian tissue. Deeply infiltrating endometriosis extends beneath the peritoneal surface and may involve adjacent pelvic organs such as the bowel or bladder, occurring in approximately 1% to 5% of affected women (6). (Figure 1).

Figure 1: An Illustration that is an overview of the three primary types of endometrioses based on lesion location: superficial peritoneal lesions, ovarian endometriomas, and deeply infiltrating endometriosis.

Comparative Evaluation of Letrozole and Danazol for Pain Reduction in Females with Endometriosis

Despite varied symptoms, endometriosis diagnosis is often delayed due to the absence of reliable non-invasive biomarkers. Current hormone therapies and analgesics offer limited long-term efficacy, as recurrence is common. Letrozole, an aromatase inhibitor, competitively binds to the cytochrome P450 subunit, reducing estrogen biosynthesis and offering a novel approach to managing endometriosis (7). Letrozole, an aromatase inhibitor, has demonstrated effectiveness in reducing endometriosis-related pain without recurrence post-treatment (8). Danazol, a synthetic androgen, suppresses ovarian activity and modulates immune function but has shown inconsistent results in pain management across studies (9). Although hormone therapies such as letrozole and danazol are widely used for symptom management, existing literature reports conflicting evidence regarding their effectiveness in reducing endometriosis-related pain. The present study seeks to answer the research question: "Among females diagnosed with endometriosis, how does the reduction in pain scores with letrozole therapy compare to danazol therapy over a three-month period, and which agent offers more consistent and sustained pain relief to inform standardized treatment protocols?" Addressing this question may improve patient outcomes in management of pain. So, this study aims to compare letrozole with danazol's impact on pain reduction in females with endometriosis, to guide future treatment protocols and update local clinical guidelines.

Enrollment

60 patients

Sex

Female

Ages

18 to 45 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Women aged 18-45 years

Surgically or clinically diagnosed endometriosis

Moderate to severe pelvic pain (NRS ≥ 4 for at least 3 months)

Willing to use effective contraception during the study

Able to provide informed consent

Exclusion criteria

  • Pregnant or breastfeeding

Severe hepatic disease, thromboembolic disorder, or contraindication to study drugs

Use of hormonal therapy within the last 8 weeks

Known hypersensitivity to Letrozole or Danazol

Participation in another clinical trial within the last 3 months

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

None (Open label)

60 participants in 2 patient groups

Arm 1: Letrozole
Experimental group
Description:
Participants in this arm will receive Letrozole 2.5 mg orally once daily for 12 weeks for management of endometriosis-related pelvic pain.
Treatment:
Drug: Letrozole
Arm 2: Danazol
Active Comparator group
Description:
Participants in this arm will receive Danazol 200 mg orally twice daily for 12 weeks for management of endometriosis-related pelvic pain.
Treatment:
Drug: danazol

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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