Comparison of Letrozole with Elagolix for the Management of Endometriosis-Associated Pain: A Quasi-Experimental Study

By Shamila Ijaz Munir, Alia Nasir-Ud-Din, Sofia Iqbal, Hina Irshad, Ujala Hussain

Affiliations

1. Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University/Sir Ganga Ram Hospital, Lahore, Pakistan

doi: 10.29271/jcpsp.2026.03.303

ABSTRACT
Objective: To compare the efficacy of Letrozole and Elagolix in the medical management of endometriosis-associated pain
Study Design: A quasi-experimental study.
Place and Duration of the Study: Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University/Sir Ganga Ram Hospital, Lahore, Pakistan, from March to August 2025.
Methodology: Women presenting with endometriosis-related pain were allocated to treatment groups. Patients in Group A (n = 29) received oral Letrozole 2.5 mg, while patients in Group B (n = 30) received oral Elagolix 150 mg once daily for three months. VAS pain scores were recorded before and 3 months post-intervention, and compared between the Letrozole and Elagolix groups using an independent samples t-test and chi-square test.
Results: Baseline data were comparable between the study groups (all p > 0.05). At 3 months post-intervention, the Elagolix group showed a significantly lower VAS score for dyspareunia (3.6 ± 2.2 vs. 4.7 ± 0.9; p = 0.016) and a greater reduction in dysmenorrhoea scores (2.2 ± 0.9 vs. 1.4 ± 1.8; p = 0.048). A shift from severe to mild was evident with significant improvements in pelvic pain (p = 0.043) and dysmenorrhoea (p = 0.036). Stratified analysis revealed significantly greater reductions in dysmenorrhea scores among Elagolix users aged ≤29 years (p = 0.025), with BMI <25 kg/m² (p = 0.013) and regular menstrual cycles (p = 0.027). Pelvic pain scores also improved significantly in participants with a monthly household income of ≥ 50,000 PKR (p = 0.037).
Conclusion: Elagolix demonstrated greater efficacy than Letrozole in reducing endometriosis-related pain after three months of treatment. This efficacy was more evident for dysmenorrhoea among specific patient subgroups, including those with younger age, lower BMI, or regular menstrual periods.

Key Words: Elagolix, Endometriosis, Letrozole, VAS pain.

INTRODUCTION

Endometriosis is a frequently encountered gynaecological condition that typically affects women during their reproductive age. This disorder is characterised by the growth of active endometrial-like tissues or glands beyond the uterine cavity, most commonly in the ovaries and peritoneal cavity.¹ Its prevalence ranges from 10% to 15% in women aged 18 to 45 years. Additionally, it accounts for approximately 33% of cases with chronic pelvic pain.² It is linked with infertility, and debilitating complaints include dyspareunia, dysmenorrhoea, and persistent pelvic pain. Other comorbid conditions include persistent pain syndrome, fatigue, depression, anxiety, autoimmune disorders, and a greater risk of certain cancers. Its diagnosis is usually delayed, ranging from 4 to 11 years after symptom onset.³

The selection of appropriate therapy is guided by pain severity, patient age, reproductive goals, and disease impact on quality of life. Symptomatic treatment strategies include both analgesic drugs and hormone-modulating therapies.⁴ First-line treatments for low to moderate endometriosis typically include nonsteroidal anti-inflammatory drugs (NSAIDs), progestin-only contraceptives (POCs), and combined hor- monal contraceptives (CHCs). If these therapies are ineffective after at least 3 months, second-line pharmacologic options, such as gonadotropin-releasing hormone (GnRH) agonist, GnRH antagonist, or aromatase inhibitor, may be considered.⁵ GnRH antagonists inhibit the production of gonadotropin by competitively blocking GnRH receptors within the hypothalamic-pituitary axis. Unlike GnRH agonists, antagonists exhibit a rapid onset of therapeutic action without inducing an initial flare-up phase and, due to their short half-life, offer swift reversibility upon discontinuation. Their non-peptide structure allows oral administration without being affected by gastrointestinal proteolysis. They decrease oestradiol concentrations in a dose-dependent manner, facilitating a balance between  therapeutic  effectiveness  and  tolerability.⁶

Elagolix, first approved by the US FDA in 2018, when adminis-tered at a low (150 mg once daily) or a high dose (200 mg twice daily), significantly improves dysmenorrhea, dyspa-reunia, and noncyclic pelvic pain.⁷ Aromatase inhibitor (AI) blocks oestrogen synthesis both peripherally and in the ovaries. Aromatase expression in endometriotic lesions and eutopic endometrium leads to local oestrogen secretion, promoting lesion growth, pain, and prostaglandin-mediated inflammation. Previous studies have demonstrated that 3^rd-generation non-steroidal AIs, such as Letrozole and Anastro-zole, have effectively reduced endometriosis-associated pain.⁵ A study conducted in China in 2020, including approxi-mately 820 patients randomly treated with Letrozole, showed a significant reduction in chronic pelvic pain, dysmenorrhea, and deep dyspareunia after six months of therapy.⁸ Another study from Pakistan reported a reduction in VAS pain scores from 7.12 to 3.3 after six months of Letrozole therapy, concluding that Letrozole effectively treated endometriosis-related pelvic pain, with significant pain relief and no symptom recurrence.⁹ On the other side, an evidence-based review supports the use of Elagolix for managing endometriosis-associated pain, including dysmenorrhea and non-menstrual pain. These results are encouraging, highlighting its tolerability and favourable safety profile.¹⁰

A review of the literature showed that both Letrozole and Elagolix have independently demonstrated promising outcomes in managing endometriosis-associated pain. However, the existing literature lacks direct comparative analyses evaluating their relative effectiveness and tolerability. Given their distinct mechanisms of action, a head-to-head evaluation may offer valuable insights into personalised therapeutic strategies. Therefore, this study aimed to compare the efficacy of Letrozole and the GnRH antagonist Elagolix in the medical management of endo-metriosis-associated pain. The findings may inform clinical decision-making, optimise symptom relief, and enhance the overall quality of life for affected individuals.

METHODOLOGY

This quasi-experimental research was conducted at the Department of Obstetrics and Gynaecology, Fatima Jinnah Medical University/Sir Ganga Ram Hospital, Lahore, Pakistan, from March to August 2025. Sixty women of reproductive age (18-45 years) who reported at least one type of endo-metriosis-related pain and had failed previous treatment were recruited using a non-probability consecutive sampling technique. Women who were pregnant or had pulmonary, cardiac, renal, or hepatic disease, or undiagnosed vaginal bleeding, were excluded. Endometriosis is a chronic inflammatory, oestrogen-dependent disease characterised by the presence and proliferation of endometrium outside the uterine cavity, as detected on transvaginal ultrasound (TVUS). Painful symptoms such as dysmenorrhoea, dyspa-reunia, and chronic pelvic pain impair the quality of life. Medical management of endometriosis aimed to achieve adequate control of pain symptoms over a prolonged period, thereby enhancing women’s quality of life and minimising the need for repeated use of surgery. Pain intensity was evaluated using a 10 cm visual analogue scale (VAS), with the left endpoint representing no pain and the right indicating the most severe pain. Scores from 1 to 4 were categorised as mild, 5 to 6 as moderate, and 7 to 10 as severe. Clinically, the amount of bleeding was characterised as low when a woman reported soaking fewer than one pad in more than 3 hours, as moderate when she reported soaking more than 1 pad in 3 hours, and as heavy when she reported soaking one or more pads every hour for several consecutive hours.

The minimum sample size for each group was determined using a mean difference of 0.16 in pelvic pain scores between the two groups,¹¹ a 95.0% confidence interval, and 80.0% test power, calculated using OpenEpi version 3. Out of 82 consecutive patients assessed for eligibility, 60 met the selection criteria and were allocated to two equal-sized independent intervention groups without randomisation. Non-random allocation was based on the physician's clinical judgment, considering patient history and preferences rather than expected costs. Patients in Group A (n = 30) received oral Letrozole 2.5 mg, and patients in Group B (n = 30) received oral Elagolix 150 mg once daily for three months. Both groups also received 1,000 mg elemental Calcium and 880 IU vitamin D daily for three months. Details are shown in the flow diagram in Figure 1.

Upon recruitment in the study, baseline demographic and clinical data, including age, BMI, occupation, income, education, residence, marital status, parity, menstrual cycle, presence and intensity of dysmenorrhoea, deep dyspareunia, and non-menstrual pelvic pain using VAS, were noted on a research proforma. The primary outcome was the comparison of the change in VAS pain scores at 3 months post-inter-vention. All women had monthly consultations during the treatment period, and side effects of each treatment protocol were recorded. The use of concomitant analgesics (including NSAIDs) was prohibited during the study period.

Data were analysed using Statistical Package for the Social Sciences (SPSS) version 26. For continuous variables, after normality assessment by Shapiro-Wilk’s test, the mean ± standard deviation (SD) was calculated and compared between the Letrozole and Elagolix groups using an independent samples t-test. For categorical variables, frequencies and percentages were calculated and compared using the chi-square test. Data were stratified by age, BMI, parity, income, marital status, and menstrual cycle. VAS pain scores were compared using the independent samples t-test or the chi-square test, as appropriate. A p-value ≤0.05 was considered statistically significant.

Table I: Baseline characteristics of study participants stratified by intervention.

Baseline characteristics		Letrozole (n = 29)		Elagolix (n = 30)		p-values
Age (years)		30.1 ± 4.2		29.7 ± 4.7		0.706
	≤29	13	44.8%	15	50.0%	0.691
	>29	16	55.2%	15	50.0%
BMI (Kg/m2)		27.9 ± 4.0		27.6 ± 3.6		0.740
	<25.0	5	17.2%	6	20.0%	0.786
	≥25.0	24	82.8%	24	80.0%
Marital status	Unmarried	6	20.7%	6	20.0%	0.996
	Married	23	79.3%	24	80.0%
Parity	0	13	44.8%	13	43.3%	0.871
	≥1	16	55.2%	17	56.7%
Occupation	Student	7	24.1%	7	23.3%	0.975
	Working	7	24.1%	8	26.7%
	Housewife	15	51.7%	15	50.0%
Residence	Urban	22	75.9%	25	83.3%	0.347
	Rural	4	13.8%	1	3.3%
	Urban slum	3	10.3%	4	13.3%
Income (PKR/month)		58586 ± 16157		56122 ± 10988		0.495
	≥50000	25	86.2%	24	80.0%	0.525
	<50000	4	13.8%	6	20.0%
Education	Illiterate	1	3.4%	2	6.7%	0.705
	Elementary	1	3.4%	3	10.0%
	Matric FA	18	62.1%	17	56.7%
	Graduate above	9	31.0%	8	26.7%
Age at menarche (years)		12.6 ± 1.2		12.3 ± 1.0		0.317
Menstrual cycle	Regular	21	72.4%	22	73.3%	0.937
	Irregular	8	27.6%	8	26.7%
Duration of menstrual cycle (days)		31 ± 4		29 ± 4		0.104
Amount of bleeding	Moderate	23	79.3%	25	83.3%	0.692
	Heavy	6	20.7%	5	16.7%
Duration of bleeding (days)		6 ± 2		6 ± 3		0.819
Duration of pelvic pain (months)		5 ± 2		6 ± 2		0.447
Infertility	No	19	65.5%	18	60.0%	0.661
	Yes	10	34.5%	12	40.0%
Duration of trying to conceive		12 ± 13		24 ± 32		0.304
Surgery for endometriosis	No	16	55.2%	19	63.3%	0.691
	Laparoscopic	8	27.6%	8	26.7%
	Laparoscopic cystectomy	5	17.2%	3	10.0%
Symptom relief	Yes	11	84.6%	9	81.8%	0.855
	Partial	2	15.4%	2	18.2%
Size of endometrioma (cm)		5.1 ± 1.3		5.2 ± 2.0		0.829
Independent samples t-test for numeric and chi-square test for categoric variables.

Table II: Comparison of VAS pain score at 3 months post-intervention.

Variables	VAS categories	Letrozole (n = 29)		Elagolix (n = 30)		p-values
Pelvic pain VAS score at 0 months	Mild	0	0.0%	0	0.0%	0.561
	Moderate	24	82.8%	23	76.7%
	Severe	5	17.2%	7	23.3%
	Mean ± SD	6.4 ± 1.0		6.5 ± 1.2		0.767
Pelvic pain VAS score at 3 months	Mild	2	6.9%	8	26.7%	0.043
	Moderate	27	93.1%	22	73.3%
	Severe	0	0.0%	0	0.0%
	Mean ± SD	4.9 ± 1.1		4.5 ± 1.4		0.169
Dysmenorrhea VAS score at 0 months	Mild	0	0.0%	0	0.0%	0.807
	Moderate	23	79.3%	23	76.7%
	Severe	6	20.7%	7	23.3%
	Mean ± SD	6.2 ± 2.0		6.6 ± 1.1		0.355
Dysmenorrhea VAS score at 3 months	Mild	1	3.4%	7	23.3%	0.036
	Moderate	26	89.7%	23	76.7%
	Severe	02	6.9%	0	0.0%
	Mean ± SD	4.8 ± 0.9		4.4 ± 1.1		0.191
Dyspareunia VAS score at 0 months (n = 47)	Mild	0	0.0%	0	0.0%	0.170
	Moderate	14	60.9%	19	79.2%
	Severe	9	39.1%	5	20.8%
	Mean ± SD	5.2 ± 3.0		5.0 ± 2.8		0.781
Dyspareunia VAS score at 3 months (n = 47)	Mild	1	4.3%	5	20.8%	0.090
	Moderate	22	95.7%	19	79.2%
	Severe	0	0.0%	0	0.0%
	Mean ± SD	4.7 ± 0.9		3.6 ± 2.2		0.016
Percentages were compared using the Pearson chi-square test, and means were compared using the independent samples t-test. Dyspareunia analysis included 47 married women (23 in the Letrozole group and 24 in the Elagolix group).

Table III: A post-stratification comparison of mean VAS pain scores.

Variables		Letrozole (n = 29)	Elagolix (n = 30)	p-values
Change in pelvic pain VAS scores	Age ≤29 years	1.6 ± 0.8	2.0 ± 1.0	0.270
	Age >29 years	1.4 ± 1.5	2.1 ± 1.1	0.158
Change in dysmenorrhoea VAS scores	Age ≤29 years	0.7 ± 2.3	2.3 ± 1.0	0.025
	Age >29 years	2.1 ± 1.0	2.1 ± 0.7	0.825
Change in dyspareunia VAS scores	Age ≤29 years	0.0 ± 2.5	1.0 ± 1.5	0.227
	Age >29 years	2.1 ± 1.1	1.9 ± 1.6	0.608
Change in pelvic pain VAS scores	BMI <25.0 Kg/m2	2.2 ± 1.3	2.8 ± 1.6	0.497
	BMI ≥25.0 Kg/m2	1.4 ± 1.2	1.9 ± 0.8	0.091
Change in dysmenorrhoea VAS scores	BMI <25.0 Kg/m2	1.2 ± 0.4	2.5 ± 0.8	0.013
	BMI ≥25.0 Kg/m2	1.5 ± 2.0	2.1 ± 0.9	0.169
Change in dyspareunia VAS scores	BMI <25.0 Kg/m2	3.0 ± 0.0	0.5 ± 1.2	0.117
	BMI ≥25.0 Kg/m2	1.3 ± 2.0	1.7 ± 1.2	0.388
Change in pelvic pain VAS scores	Unmarried	1.5 ± 0.8	2.3 ± 1.2	0.196
	Married	1.5 ± 1.3	2.0 ± 1.0	0.169
Change in dysmenorrhoea VAS scores	Unmarried	0.5 ± 2.7	2.5 ± 1.0	0.031
	Married	1.9 ± 1.1	2.1 ± 0.9	0.560
Change in dyspareunia VAS scores	Unmarried	-	-	-
	Married	1.8 ± 1.2	1.8 ± 1.2	0.984
Change in pelvic pain VAS scores	Parity 0	1.1 ± 1.3	1.8 ± 0.7	0.145
	Parity ≥1	2.0 ± 1.2	2.3 ± 1.3	0.626
Change in dysmenorrhoea VAS scores	Parity 0	2.2 ± 1.0	2.2 ± 0.9	1.000
	Parity ≥1	1.6 ± 1.2	2.0 ± 0.8	0.364
Change in dyspareunia VAS scores	Parity 0	1.8 ± 1.2	1.7 ± 1.5	0.887
	Parity ≥1	1.9 ± 1.2	2.0 ± 0.8	0.821
Change in pelvic pain VAS scores	Income ≥50,000 PKR	1.4 ± 1.3	2.2 ± 1.1	0.037
	Income <50,000 PKR	1.8 ± 0.5	1.5 ± 0.8	0.610
Change in dysmenorrhoea VAS scores	Income ≥50,000 PKR	1.4 ± 2.0	2.3 ± 0.9	0.058
	Income <50,000 PKR	1.8 ± 0.5	2.0 ± 0.9	0.629
Change in dyspareunia VAS scores	Income ≥50,000 PKR	1.2 ± 2.1	1.5 ± 1.2	0.552
	Income <50,000 PKR	2.0 ± 0.8	1.2 ± 1.7	0.399
Change in pelvic pain VAS scores	MC regular	1.7 ± 1.1	2.1 ± 1.2	0.141
	MC irregular	1.3 ± 1.6	1.8 ± 0.5	0.294
Change in dysmenorrhoea VAS scores	MC regular	1.1 ± 1.9	2.1 ± 0.9	0.027
	MC irregular	2.5 ± 0.9	2.5 ± 0.8	1.000
Change in dyspareunia VAS scores	MC regular	1.1 ± 2.2	1.2 ± 1.2	0.845
	MC irregular	1.9 ± 1.4	2.1 ± 1.4	0.718
Independent samples t-test.

Figure 1: CONSORT flow diagram.

RESULTS

Data from a total of 59 women, 29 in the Letrozole group and 30 in the Elagolix group, who completed the study were analysed. The distribution of baseline characteristics was similar between the two groups (all p >0.05; Table I).

The distribution of no family history of endometriosis [22 (75.9%) vs. 22 (73.3%)], no history of past surgery [21 (72.4%) vs. 20 (66.7%)], and no previous diagnosis by laparoscopy [20 (69.0%) vs. 21 (70.0%)] were similar between the two study groups (Figure 2A, B).

Baseline mean VAS scores and pain severity distributions for pelvic pain, dysmenorrhoea, and dyspareunia were comparable between the Letrozole and Elagolix groups (all p >0.05). At 3 months post-intervention, the Elagolix group achieved a significantly better distribution of pain severity compared to the Letrozole group. Specifically, a significantly higher proportion of women in the Elagolix group shifted to mild status for both pelvic pain (p = 0.043) and dysmenorrhoea (p = 0.036). Additionally, the Elagolix group demonstrated a significantly greater reduction in dysmenorrhea VAS score (2.2 ± 0.9 vs. 1.4 ± 1.8; p = 0.048), while the reduction in pelvic pain (2.1 ± 1.0 vs. 1.5 ± 1.2; p = 0.068) and dyspareunia (1.5 ± 1.3 vs. 1.4 ± 2.0; p = 0.812) did not reach statistical significance. The mean VAS scores for pelvic pain (p = 0.169) and dysmenorrhoea (p = 0.191) were not statistically different at 3 months. In contrast, for dyspareunia, the Elagolix group demonstrated a significantly lower mean VAS score at 3 months compared to the Letrozole group (3.6 ± 2.2 vs. 4.7 ± 0.9; p = 0.016). Although the shift toward the mild pain category was more distinct in the Elagolix group, this distribution change was not statistically significant (p = 0.090; Table II).

Figure 2 (A, B): Clinical features of study participants stratified by intervention. (A) History of endometriosis. (B) Pelvic pain association.

In the post-stratification comparative analysis, the Elagolix group showed a significantly greater reduction in dysmenorrhea VAS scores among participants aged ≤29 years (p = 0.025), those with a BMI <25 kg/m² (p = 0.013), and those reporting a regular menstrual cycle (p = 0.027). Additionally, the Elagolix group demonstrated a significantly greater reduction in pelvic pain VAS scores among participants with a monthly household income ≥50,000 PKR (p = 0.037). However, no significant differences were observed in dyspareunia VAS scores between the two groups (all p >0.05; Table III).

DISCUSSION

Endometriosis affects many women of reproductive age and often leads to chronic pelvic pain and infertility. These symptoms can seriously reduce quality of life, highlighting the need for effective treatment strategies.¹ Endometriosis-related pain involves different mechanisms; therefore, careful evaluation is needed to confirm the diagnosis and rule out other possible causes. Both medical and surgical treatments are available and effective; however, the choice of treatment should be personalised according to the patients’ condition.¹² Medical therapy in endometriosis aims to lower oestrogen levels, thereby limiting retrograde menstruation, addressing progesterone resistance, and reducing inflammation. It also seeks to inhibit aromatase expression while promoting anti-angiogenic and immunoregulatory effects. In a systematic review and meta-analysis, Chaichian et al. compared the effectiveness of both methods and found no statistically significant difference in pain improvement. The authors concluded that the results did not show a clear preference between medical or surgical treatment for dysmenorrhoea in endometriosis. They recommended that clinicians consider less invasive options when treating chronic pelvic pain.¹³

According to Ezzati et al., the main goal of medical treatment is to suppress oestrogen production and reduce menstrual spill.¹⁴ This is usually achieved through CHCs, GnRH analogues, and progestin. These treatments have similar effectiveness but different safety profiles. Elagolix is a leading drug among the newly developed GnRH antagonists. Unlike older peptide-based drugs, Elagolix has a non-peptide structure, which makes it available in oral form. Phase I and II clinical trials demonstrated that Elagolix was safe and effective in partially and reversibly suppressing ovarian oestrogen production, leading to improvement in endometriosis-associated pain.¹⁴ Taylor et al. also showed that Elagolix significantly decreased dysmenorrhoea and non-menstrual pelvic pain among women with moderate to severe endometriosis.¹¹ The present study compared the effectiveness of Letrozole with Elagolix in treating endo-metriosis-associated pain and found that Elagolix was significantly more effective in reducing pelvic pain and dysmenorrhea after six months of treatment. These findings align with previous studies and support the use of Elagolix as a first-line medical treatment. In endometriosis-associated infertility, Elagolix established a statistically significant reduction in dyspareunia score,^15,16 while minimising adverse effects.

On the other hand, AIs are used as second-line therapy for managing endometriosis-related pelvic pain.¹⁷ Some studies suggest that Letrozole, especially when combined with progestins or oral contraceptives, can reduce pain, but its effectiveness as a single treatment is limited. In a network meta-analysis, Csirzo et al. found that for dysmenorrhoea, GnRH agonists combined with hormonal contraceptives reduced pain after three months. For dyspareunia, hormonal contraceptives were most effective. For overall pelvic pain, hormonal contraceptives or progestins combined with aromatase inhibitors gave the best results.¹⁸ Ferrero et al. confirmed that Letrozole is effective in treating pain caused by rectovaginal endometriosis. Their study showed that combining Letrozole with progestin was better accepted by patients. Combining aromatase inhibitors with GnRH analogues may cause more side effects.¹⁹ In contrast, Qureshi et al. reported a mean VAS pain score dropped from 7.12 at the start of therapy to 3.3 after six months of treatment. The authors concluded that Letrozole was effective in reducing pelvic pain with no recurrence of symptoms.⁹ Nawaz et al. reported a mean VAS pain score dropped from 5.46 ± 1.09 to 2.94 ± 1.96 in the Letrozole group and from 5.28 ± 1.01 to 3.99 ± 1.90 in the Danazol group (p = 0.002). The authors concluded that Letrozole was more effective than Danazol in relieving pain in endometriosis patients.²⁰ In the present study, Letrozole was less effective than Elagolix in reducing pain, suggesting that peripheral oestrogen suppression via aromatase inhibition may not be sufficient to control pain symptoms in all patients. The lack of combination therapy in the Letrozole group may have contributed to its comparatively lower efficacy.

Despite the promising results, this research study has some limitations. The association of higher income with improved pelvic pain relief, specifically within the Elagolix group, suggests that socioeconomic status may enhance treatment effectiveness. This is likely due to factors known to moderate chronic pain outcomes, such as improved treatment adherence and better access to supportive care. The small sample size may limit the generalisability of the results. Additionally, long-term outcomes could not be assessed due to the short study duration. Letrozole was administered as monotherapy, and future studies should explore its efficacy in combination with other hormonal agents. Other limitations include the lack of formal assessment of treatment compliance, a short follow-up, and the absence of formal assessment of adverse events.

CONCLUSION

Elagolix was more effective than Letrozole in reducing endometriosis-related pain after three months of treatment. It demonstrated better efficacy by providing a significantly greater reduction in dysmenorrhoea and achieving a significantly lower final score for dyspareunia. This effect was more evident for dysmenorrhoea in specific patient subgroups, including younger women, those with lower BMI, regular menstrual cycles, or higher household income. These results suggest Elagolix can be a valuable therapeutic option for managing endometriosis-related pain, particularly dysme- norrhoea.

ETHICAL APPROVAL:
Ethical approval was obtained from the Ethical Review Committee of the Fatima Jinnah Medical University, Lahore, Pakistan (letter No. 190-Synopsis-ERC; dated: 27^th February 2025).

PATIENTS’ CONSENT:
Written informed consent was sought from all volunteer women, ensuring autonomy, confidentiality, and the right to withdraw at any time.

COMPETING INTEREST:
The authors declared no conflict of interest.

AUTHORS’ CONTRIBUTION:
SIM: Study conception, design, and supervision, manuscript revision, and final approval; accountable for submission.
ANUD: Study design, data entry and analysis, drafting and final approval; accountable for the submission.
SI, HI, UH: Data collection and interpretation, editing, and review.
All authors approved the final version of the manuscript to be published.

REFERENCES

1. Saleem Azam S, Vasudevan S, Saqib Bukhari W, Thadhani J, Tasneem H, Singh S, et al. Reproductive endocrine disorders: A comprehensive guide to the diagnosis and management of infertility, polycystic ovary syndrome, and endo-metriosis. Cureus 2025; 17(1):e78222. doi: 10.7759/cureus. 78222.
2. Zondervan KT, Becker CM, Missmer SA. Endometriosis. N Engl J Med 2020; 382(13):1244-56. doi: 10.1056/NEJMra 1810764.
3. Taylor HS, Kotlyar AM, Flores VA. Endometriosis is a chronic systemic disease: Clinical challenges and novel innovations. Lancet 2021; 397(10276):839-52. doi: 10.1016/S0140- 6736(21)00389-5.
4. Chapron C, Marcellin L, Borghese B, Santulli P. Rethinking mechanisms, diagnosis and management of endometriosis. Nat Rev Endocrinol 2019; 15(11):666-82. doi: 10.1038/ s41574-019-0245-z.
5. Vannuccini S, Clemenza S, Rossi M, Petraglia F. Hormonal treatments for endometriosis: The endocrine background. Rev Endocr Metab Disord 2022; 23(3):333-55. doi: 10.1007/ s11154-021-09666-w.
6. Resta C, Moustogiannis A, Chatzinikita E, Malligiannis Ntalianis D, Malligiannis Ntalianis K, Philippou A, et al. Gonadotropin-releasing hormone (GnRH)/GnRH receptors and their role in the treatment of endometriosis. Cureus 2023; 15(4):e38136. doi: 10.7759/cureus.38136.
7. Leyland N, Estes SJ, Lessey BA, Advincula AP, Taylor HS. A clinician's guide to the treatment of endometriosis with Elagolix. J Womens Health (Larchmt) 2021; 30(4):569-78. doi: 10.1089/jwh.2019.8096.
8. Zhao Y, Luan X, Wang Y. Letrozole combined with oral contraceptives versus oral contraceptives alone in the treatment of endometriosis-related pain symptoms: A pilot study. Gynecol Endocrinol 2021; 37(1):51-5. doi: 10.1080/09513 590.2020.1807502.
9. Qureshi Q, Sadaf M, Rukhsana RA, Dileep A, Shahani MP. Letrozole, for the management of chronic pelvic pain resulting from endometriosis. Pak J Med Health Sci 2023; 17(3):526-7. doi: 10.53350/pjmhs2023173526.
10. Urits I, Adamian L, Miro P, Callan J, Patel PM, Patel M, et al. An evidence-based review of elagolix for the treatment of pain secondary to endometriosis. Psychopharmacol Bull 2020; 50(4 Suppl 1):197-215. doi: 10.64719/pb.4390.
     
11. Taylor HS, Giudice LC, Lessey BA, Abrao MS, Kotarski J, Archer DF, et al. Treatment of endometriosis-associated pain with elagolix, an oral GnRH antagonist. N Engl J Med 2017; 377(1):28-40. doi: 10.1056/NEJMoa1700089.
12. Practice Committee of the American Society for Reproductive Medicine. Treatment of pelvic pain associated with endometriosis: A committee opinion. Fertil Steril 2014; 101(4):927-35. doi: 10.1016/j.fertnstert.2014.02.012.
13. Chaichian S, Kabir A, Mehdizadehkashi A, Rahmani K, Moghimi M, Moazzami B. Comparing the efficacy of surgery and medical therapy for pain management in endometriosis: A systematic review and meta-analysis. Pain Physician 2017; 20(3):185-95. doi: 10.36076/ppj.2017.195.
14. Ezzati M, Carr BR. Elagolix, a novel, orally bioavailable GnRH antagonist under investigation for the treatment of endometriosis-related pain. Womens Health (Lond) 2015; 11(1):19-28. doi: 10.2217/whe.14.68.
15. Musa S, Osman S. Risk profile of Qatari women treated for infertility in a tertiary hospital: A case-control study. Fertil Res Pract 2020; 6(1):12. doi: 10.1186/s40738-020-00 080-5.
     
16. Garzon S, Lagana AS, Barra F, Casarin J, Cromi A, Raffaelli R, et al. Aromatase inhibitors for the treatment of endo-metriosis: A systematic review about efficacy, safety and early clinical development. Expert Opin Investig Drugs 2020; 29(12):1377-88. doi: 10.1080/13543784.2020.1842356.
17. Patel M. Recent trends in medical management of endometriosis. J Obstet Gynaecol India 2024; 74(6):479-83. doi: 10.1007/s13224-024-02097-y.
18. Csirzo A, Kovacs DP, Szabo A, Szabo B, Janko A, Hegyi P, et al. Comparative analysis of medical interventions to alleviate endometriosis-related pain: A systematic review and network meta-analysis. J Clin Med 2024; 13(22):6932. doi: 10.3390/jcm13226932.
19. Ferrero S, Venturini PL, Gillott DJ, Remorgida V. Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: A randomized controlled trial. Reprod Biol Endocrinol 2011; 9:88. doi: 10.1186/1477-7827-9-88.
20. Nawaz S, Habib S, Ayoub S, Shams G, Naeem N, Sultana R. Comparison of the efficacy of letrozole versus danazol in pain relief in endometriosis: Efficacy of letrozole and danazol in endometriosis. Pak J Health Sci 2022; 3(6):248-52. doi: 10.54393/pjhs.v3i06.345.