Nonsteroidal anti-inflammatory drug resistance in dysmenorrhea: a study of prevalence, predictors, and alternative pain management among Nigerian female students

Abstract

Background

Dysmenorrhea is a common gynaecological condition among young women, with non-steroidal anti-inflammatory drugs (NSAIDs) recommended as first-line therapy. However, a substantial proportion of women experience inadequate pain relief despite NSAID use. This study aimed to determine the prevalence of NSAID-resistant dysmenorrhea and to identify predictors as well as alternative pain management strategies among female undergraduate students at Afe Babalola University, Ado-Ekiti, Nigeria (ABUAD).

Methods

A descriptive cross-sectional study was conducted among 271 female undergraduate students of ABUAD. Data were collected using a structured, self-administered electronic questionnaire that assessed socio-demographic characteristics, menstrual history, dysmenorrhea severity, NSAID use, perceived effectiveness, and alternative pain management strategies. NSAID-resistant dysmenorrhea was operationally defined as persistent menstrual pain despite reported use of recommended NSAID dosages. Descriptive statistics were used to summarize data. Bivariate analyses were conducted using Chi-square, Fisher’s exact, and Mann–Whitney U tests, as appropriate. Multivariate logistic regression was performed to identify independent predictors of NSAID resistance. Statistical significance was set at p ≤ 0.05.

Results

The prevalence of dysmenorrhea among participants was 70.8% (192/271). Of those with dysmenorrhea, 62.5% (120/192) reported NSAID use for pain management. Among NSAID users, 63 students were classified as having NSAID-resistant dysmenorrhea, representing 52.5% of NSAID users and 32.8% of all students with dysmenorrhea. Perceived delayed onset of NSAID action (adjusted odds ratio [AOR] = 16.91; 95% CI: 2.00–141.60; p = 0.009) and lower NSAID effectiveness scores (AOR = 0.72; 95% CI: 0.57–0.90; p = 0.004) were significant predictors of NSAID resistance. Common coping strategies among NSAID-resistant students included activities such as use of alternative medications (25.4%), NSAID dose escalation (23.8%), rest or sleep (6.3%), as well as medications including antispasmodics (31.7%), and herbal remedies (11.2%).

Conclusion

NSAID-resistant dysmenorrhea is common among undergraduate students. Perceived delayed onset and reduced effectiveness of NSAIDs are key predictors of resistance and contribute to reliance on alternative and potentially unsafe coping strategies. These findings highlight the need for improved education on appropriate dysmenorrhea management, early identification of NSAID non-responders, and access to evidence-based alternative treatment options.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12978-026-02404-y.

Plain language summary

Painful menstruation (dysmenorrhea) is common among young women and can affect daily activities and academic performance. Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and diclofenac, are commonly used to treat menstrual pain. However, some women do not experience adequate relief even when these medicines are taken correctly.

This study investigated how often menstrual pain does not respond to NSAIDs, the predictors of poor response, and the alternative ways students manage their pain. The study included 271 female undergraduate students at Afe Babalola University in Nigeria.

Most participants reported experiencing menstrual pain, and many used NSAIDs for relief. However, more than half of NSAID users reported that the medicines did not adequately relieve their pain, even when taken at the recommended doses. Overall, nearly one in three students with menstrual pain was classified as having NSAID-resistant dysmenorrhea. Many students reported that NSAIDs worked too slowly or were ineffective. When NSAIDs did not relieve pain, students often used other strategies such as increasing NSAID doses without medical advice, taking other pain medicines, resting, using heat therapy, herbal remedies, or visiting the hospital. Students who perceived NSAIDs as slow or ineffective were more likely to have NSAID-resistant menstrual pain, while factors such as age and menstrual characteristics were not strongly associated.

These findings highlight the need for better education on safe pain management, early identification of students who do not respond to NSAIDs, and improved access to effective treatment options for menstrual pain.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s12978-026-02404-y.

Background

Dysmenorrhea, commonly referred to as painful menstruation, is characterized by cramping pain in the lower abdomen that occurs shortly before or during menstruation and may be accompanied by systemic symptoms such as nausea, vomiting, diarrhoea, headache, fatigue, and sweating [1]. It is one of the most frequently reported gynaecological complaints among women of reproductive age, typically defined as females aged 15–49 years [2, 3]. Undergraduate students, who are generally within the late adolescent and young adult age range (approximately 16–30 years), therefore fall squarely within this reproductive age bracket, making dysmenorrhea a particularly relevant health concern in this population [2, 3].

Globally, dysmenorrhea represents a substantial public health burden, with reported prevalence ranging from 50% to over 90% depending on age, population, and diagnostic criteria [2]. The condition is especially prevalent among adolescents and young adults, with studies consistently reporting higher rates among women aged 17–25 years [2]. Dysmenorrhea significantly impairs quality of life, affecting academic performance, work productivity, social functioning, and psychological wellbeing. In addition to personal suffering, it contributes to considerable economic losses through healthcare costs, absenteeism, and reduced productivity [4].

In Nigeria, dysmenorrhea is also found to be highly prevalent among young women. A study among Nigerian undergraduates reported that 69.8% experienced dysmenorrhea, yet many did not seek medical care and instead relied on self-medication or ignored the pain [5].

Knowledge and attitudes toward dysmenorrhea have also been shown to be suboptimal, with a substantial proportion of students demonstrating poor understanding of the condition and negative perceptions toward seeking treatment [6, 7]. These findings highlight the need for improved pain management strategies and targeted research among undergraduate populations.

Primary dysmenorrhea, which occurs in the absence of identifiable pelvic pathology, is influenced by a complex interplay of biological, behavioural, and psychosocial factors. Established risk factors include young age, nulliparity, early menarche, heavy or prolonged menstrual bleeding, low or high body mass index, smoking, and family history of dysmenorrhea [8]. Psychological factors such as stress, anxiety, depression, and somatization have also been consistently associated with increased pain severity and poorer pain coping [9]. Among undergraduate students, academic stress, irregular sleep patterns, dietary changes, limited physical activity, and high reliance on self-medication may further exacerbate menstrual pain and influence treatment outcomes, making this population uniquely vulnerable [10].

The management of primary dysmenorrhea is primarily symptomatic, with the goal of achieving adequate pain relief and improving daily functioning. Pharmacological treatment remains the cornerstone of therapy, with non-steroidal anti-inflammatory drugs (NSAIDs) widely recommended as first-line agents due to their inhibition of prostaglandin synthesis [11, 12]. Hormonal contraceptives are considered second-line therapy and act by suppressing ovulation and reducing endometrial prostaglandin production [13]. Other pharmacological and non-pharmacological interventions, including vitamins, omega-3 fatty acids, heat therapy, exercise, and transcutaneous electrical nerve stimulation, have demonstrated variable effectiveness [14, 15].

Despite their established efficacy, evidence from both clinical trials and population-based studies indicates that a notable proportion of women do not achieve satisfactory pain relief with NSAIDs. Systematic reviews have reported that approximately 18–25% of patients with dysmenorrhea experience inadequate or no pain relief following NSAID use [16, 17]. These findings are corroborated by observational studies in diverse populations. Among university students in Ibadan, Nigeria, 11.6% reported that NSAIDs were ineffective in managing their dysmenorrhea [18], while a lower prevalence of 4.2% was reported among university students in Borno State [19]. Outside Nigeria, a population-based study in the United States reported that between 29.3% and 35.6% of women perceived NSAID treatment for dysmenorrhea to be ineffective [20]. Similarly, reduced effectiveness or absence of pain relief following NSAID use has been reported among secondary school students in Mexico [21, 22]. Collectively, these findings highlight that NSAID non-response is a consistent and clinically relevant phenomenon across different age groups and geographic settings.

This phenomenon has been described in the literature using terms such as NSAID non-response, treatment failure, ineffectiveness, or poor analgesic response, and is increasingly conceptualized as NSAID-resistant dysmenorrhea [17–22]. Proposed mechanisms underlying this resistance include delayed onset of action, poor adherence, pharmacokinetic variability affecting drug bioavailability, genetic polymorphisms influencing cyclooxygenase (COX-1/COX-2) activity, and prostaglandin-independent pathways of uterine contractility [17]. In response to inadequate pain relief, many women adopt alternative or potentially unsafe coping strategies, including increasing NSAID doses beyond recommended limits, combining multiple analgesics, or using non-prescribed alternatives such as herbal products and antispasmodics [23–25].

Despite growing recognition of NSAID treatment failure in dysmenorrhea, there remains a paucity of studies explicitly assessing NSAID-resistant dysmenorrhea as a defined outcome, particularly in low- and middle-income countries like Nigeria. Most existing studies carried out in Nigeria have focused on the general prevalence of dysmenorrhea or overall treatment patterns [5, 26–28], with limited attention to patient-perceived effectiveness, behavioural responses to treatment failure, and predictors of NSAID resistance among young women. This gap is more pronounced among undergraduate populations in Nigeria, where self-medication is common and access to specialized care may be limited.

Therefore, this study was designed to address this important gap by assessing the prevalence of NSAID-resistant dysmenorrhea, identifying alternative treatment strategies employed when NSAIDs are ineffective, and determining predictors of NSAID resistance among female undergraduate students at Afe Babalola University, Ado-Ekiti, Nigeria. By focusing on this population, the study aims to generate context-specific evidence that can inform more effective, safer, and patient-centred approaches to dysmenorrhea management.

Methods

Study design and duration

The study was as a cross-sectional study carried out between November 2023 to April 2024.

Study site

The study was conducted at ABUAD, a private tertiary institution with a collegiate system comprising six colleges: College of Medicine and Health Sciences, College of Pharmacy, College of Law, College of Engineering, College of Sciences, and College of Social and Management Sciences. The university operates a centralized healthcare system through its university hospital, where students predominantly access medical care and prescription medications, and self-medication is relatively limited due to institutional regulations.

Study population

The study population comprised female undergraduate students enrolled in any of the six colleges at ABUAD during the study period. At the time of the study, the university had an estimated total female undergraduate population of 4845 students, who constituted the sampling frame for this research.

Inclusion and exclusion criteria

Female undergraduate students of ABUAD aged 16 years and above, who were currently menstruating and willing to provide informed consent were eligible to participate in the study. The inclusion of students aged 16–17 years reflects the Nigerian university admission policy, where the minimum entry age into undergraduate programmes is 16 years. Students who were pregnant, menopausal, or had medical conditions associated with amenorrhea (such as hysterectomy or endocrine disorders) were excluded to avoid confounding the assessment of dysmenorrhea. Additionally, participants who declined consent, withdrew participation at any stage, or submitted incomplete questionnaires were excluded from the final analysis.

Sample size determination

The minimum sample size for this study was determined using the Raosoft^® online sample size calculator (Raosoft Inc., Seattle, WA, USA) [29]. Based on an estimated total female undergraduate population of 4,845 students, obtained through consultation with the administrative offices of all colleges within the university, the following parameters were applied: a 95% confidence level, a 5% margin of error, and an assumed response distribution of 18%, derived from the prevalence of inadequate NSAID response reported in previous clinical studies [17]. Using these assumptions, the calculated minimum required sample size was 217 participants. At the conclusion of data collection, a total of 271 fully completed questionnaires were obtained and included in the final analysis.

Sampling technique and recruitment procedure

A non-probability sampling approach, combining convenience sampling and snowball sampling, was used due to logistics concerns. Prior to the sampling of the colleges, a proportionate allocation was done to estimate the number of participants to be sampled per college. This has been summarised in Table 1. All six colleges in the university were included. Each college was physically visited by the research team, during which meetings were held with Heads of Departments and class representatives. The purpose and procedures of the study were explained, and permission was obtained to share the survey link within official departmental and class WhatsApp groups across all academic levels. The Google Forms^® questionnaire link (Google LLC, United States) was then distributed through these WhatsApp groups.

Table 1.

Proportionate allocation of sample

COLLEGE	POPULATION	SAMPLE
Pharmacy	562	25
Law	890	40
MHS	2303	103
Engineering	405	18
SMS	345	15
Sciences	340	15
TOTAL	4845	217

Participants were encouraged to share the link with eligible peers within their colleges, facilitating snowball recruitment.

Instrument for data collection

Data were collected using a structured, self-administered electronic questionnaire developed after a thorough review of relevant literature on dysmenorrhea and NSAID use [5, 23–28]. The questionnaire was designed using Google Forms^® (Google LLC, United States) and comprised 21 items organized into five sections, aligned with the study objectives [Additional File 1].

Section A: Demographic and menstrual characteristics (9 items)

This section collected information on participants’ sociodemographic and menstrual characteristics, including age, college, department, level of study, religion, ethnicity, age at menarche, menstrual cycle length, and duration of menstrual flow.

Section B: Dysmenorrhea assessment (2 items)

This section assessed the presence of dysmenorrhea and the severity of menstrual pain. Participants were asked whether they experienced dysmenorrhea (Yes/No). Those who reported dysmenorrhea rated their menstrual pain intensity on a numeric rating scale ranging from 1 to 10, where scores of 1–3 indicated mild pain, 4–6 indicated moderate pain, and 7–10 indicated severe pain. A brief standardized definition of dysmenorrhea was provided to ensure uniform understanding among participants at the beginning of the questionnaire.

Section C: Management of dysmenorrhea and NSAID resistance (5 items)

This section evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and assessed NSAID-resistant dysmenorrhea. Participants were asked about NSAID use for menstrual pain management, adherence to a recommended dosage, perceived effectiveness of NSAIDs, and delayed onset of pain relief. In this questionnaire, recommended dosage was defined as taking the correct dose, at the right frequency, for the correct duration as prescribed by a healthcare professional. NSAID resistance was operationalized based on self-reported NSAID use, adherence to the recommended dosage, and persistent pain despite adherence. The questions had binary response format in form of yes/no.

Section D: Alternative pain management strategies (2 items)

Participants reported actions taken when NSAIDs failed to provide adequate relief, including dose escalation, use of alternative medications, hospital visits, and non-pharmacological or pharmacological alternatives such as antispasmodics, hormonal contraceptives, and herbal remedies. Multiple responses were permitted where applicable.

Section E: Factors associated with dysmenorrhea (3 items)

This section assessed selected health and lifestyle factors potentially associated with dysmenorrhea and NSAID resistance, including physical activity, tobacco use, and the presence of chronic medical conditions such as endometriosis or uterine fibroids. Responses were recorded as Yes/No.

NSAID resistance assessment

The prevalence of NSAID-resistant dysmenorrhea was determined using a set of targeted items within the questionnaire. Participants were sequentially asked whether they:

• Experienced dysmenorrhea, to identify those with menstrual pain.

• Used NSAIDs (e.g., ibuprofen, naproxen, diclofenac, piroxicam) for the management of menstrual pain.

• Adhered to the recommended NSAID dosage when managing dysmenorrhea, defined as using the medication at the dose and duration prescribed by a healthcare professional.

• Experienced inadequate pain relief despite using NSAIDs at the recommended dosage.

• Perceived a delayed onset of analgesic effect following NSAID use.

Participants who reported NSAID use, adherence to the recommended dosage, and persistent menstrual pain despite use at recommended dosage were classified as having NSAID-resistant dysmenorrhea. NSAID-resistant dysmenorrhea was determined using a predefined three-item scoring algorithm was used. Participants who reported experiencing dysmenorrhea were assessed using three dichotomous (Yes/No) items: (1) use of nonsteroidal anti-inflammatory drugs (NSAIDs) for the management of menstrual pain, (2) adherence to a healthcare professional-recommended NSAID dosage—defined as taking the correct dose, at the appropriate frequency, and for the recommended duration—and (3) persistence of menstrual pain despite NSAID use at the recommended dosage. Each affirmative (“Yes”) response was assigned one point, yielding a total possible score ranging from 0 to 3. Participants who scored the maximum of three points (3/3) were classified as having NSAID-resistant dysmenorrhea. Participants with scores less than three were classified as non-NSAID-resistant. Perceived delayed onset of NSAID analgesic effect was assessed separately to further characterize patterns of reduced NSAID effectiveness but was not included in the resistance classification.

Measurement rationale

In this study, recommended dosage referred to the appropriate dose, dosing interval, and duration of NSAID therapy as prescribed or recommended by a healthcare professional, rather than self-selected or empirically adjusted dosing. This operational definition was adopted to enhance clarity and ecological validity within the study setting.

Afe Babalola University operates a centralized campus health system, where students typically obtain analgesics and other medications through professional consultation and where unsupervised self-medication is restricted. Consequently, wide variability in dosing practices is minimized, making a standardized, prescription-based definition appropriate for estimating NSAID resistance.

Drug-specific dosage thresholds were intentionally not specified due to the heterogeneity of NSAIDs used and to reduce recall burden among participants. Although timing and frequency of NSAID administration were not independently quantified, the institutional care model reduces variability in medication use patterns. While self-report may introduce response bias, restricting the resistance classification to ineffectiveness despite recommended use was intended to improve specificity for pharmacologic non-response.

Validity and reliability of the instrument

Content validity were established through review by experts who were lecturers in the Department of Clinical Pharmacy and Public Health at ABUAD. Revisions were made based on their recommendations to improve clarity and relevance. A pretest was conducted among 10 female undergraduate students from the College of Pharmacy, selected conveniently. These students were excluded from the final analysis. Internal consistency reliability was assessed only for the dichotomous NSAID resistance items using the Kuder–Richardson Formula 20 (KR-20). Items measured on continuous scales (e.g., NSAID effectiveness rated on a 0–10 numeric scale) were excluded from the reliability analysis, as KR-20 is appropriate only for binary response formats. A coefficient of 0.78 was obtained after the analysis.

Data analysis

Data were analysed using descriptive statistics, bivariate tests, and multivariate logistic regression using SPSS version 27.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics, including frequencies, percentages, means, and standard deviations, were used to summarize participants’ sociodemographic characteristics, menstrual characteristics, and NSAID use patterns.

The prevalence of NSAID-resistant dysmenorrhea was estimated by calculating the proportion of respondents who met the study’s operational definition of NSAID resistance that is, participants who reported experiencing dysmenorrhea, using NSAIDs for menstrual pain, adhering to a healthcare professional-prescribed (recommended) dosage, and still reporting inadequate pain relief. This proportion was expressed as a percentage of all participants who reported dysmenorrhea.

For bivariate analysis, Chi-square test or Fisher-Freeman-Halton Exact test was used to examine associations between NSAID resistance and categorical variables, while the Mann–Whitney U test was applied for comparisons involving continuous variables that were not normally distributed. Variables with a p-value < 0.20 in bivariate analysis, as well as variables considered clinically relevant based on prior literature (including age, age at menarche, menstrual cycle length, duration of menstrual flow, and presence of chronic medical conditions), were selected for multivariate analysis.

Multivariate binary logistic regression was conducted to identify independent predictors of NSAID-resistant dysmenorrhea. The dependent variable was NSAID resistance (Yes/No). Independent variables included perception that NSAIDs take too long to provide pain relief (Yes/No) and menstrual pain intensity (entered as a continuous or categorized variable). Age, age at menarche, menstrual cycle length, duration of menstrual flow, and chronic medical conditions were included as control variables. Smoking status and physical activity were excluded from the final model due to limited variability and lack of statistical significance in bivariate analysis.

Adjusted odds ratios (ORs) with 95% confidence intervals (CIs) were reported, and statistical significance was set at p ≤ 0.05.

Ethical considerations and informed consent

Ethical approval for the study was obtained from the Afe Babalola University Research Ethics Committee (ABUADREC) (Approval number: ABUADHREC/19/12/2023/24; Date: 12/10/2023). Permission to conduct the study within the university was additionally obtained through administrative engagement with relevant academic units.

The Google Forms questionnaire opened with a study introduction and an electronic informed consent statement. Participants were required to actively indicate consent before accessing the questionnaire. Those who did not provide consent were automatically exited from the form, and no data were collected from them. Participation was voluntary, and respondents were informed of their right to withdraw at any point before submission without penalty.

Results

Demographics

Table 2 presents the socio-demographic, menstrual, and health characteristics of the study participants. A total of 271 female undergraduate students participated in this study, with a mean age of 19.62 ± 1.70 years (range: 16–25 years). The majority of participants were Christians (237, 87.5%), and the most common ethnic group was Yoruba (121, 44.6%). Most were enrolled in the College of Medicine and Health Sciences (109, 40.2%) and the College of Pharmacy (91, 33.6%). Students in their 400-level constituted the largest proportion of the sample (83, 30.6%), followed by those in 500-level (71, 26.2%) and 300-level (58, 21.4%). Regarding menstrual characteristics, the mean age at menarche was 12.0 ± 1.46 years, while the mean menstrual cycle length and duration of menstrual flow were 27.95 ± 2.48 days and 4.81 ± 1.12 days, respectively. Dysmenorrhea was reported by 192 students (70.8%) among which more than half reported severe menstrual pain (101, 52.6%), while 12 (6.3%) reported mild pain. In this subgroup, 77 students (40.1%) reported engaging in regular physical activity, whereas the vast majority did not smoke (191, 99.5%). The breakdown of the distribution of the participants based on departments and levels has been summarised in Additional File 2.

Table 2.

Socio-demographic, menstrual, and health characteristics of the students

Demographics (N = 271)		Frequency	Percent
Age (Mean ± SD)		19.62 ± 1.704 years (Range: 16–25 years)
Religion	Christianity	237	87.5
	Islam	34	12.5
Ethnicity	Yoruba	121	44.6
	Igbo	71	26.2
	Hausa	9	3.3
	Others	70	25.8
College	MHS	109	40.2
	Pharmacy	91	33.6
	Law	40	14.8
	Engineering	5	1.8
	Sciences	11	4.1
	SMS	15	5.5
Level of study	100 Level	4	1.5
	200 Level	54	19.9
	300 Level	58	21.4
	400 Level	83	30.6
	500 Level	71	26.2
	600 Level	1	0.4

Menstrual Characteristics (N = 271)
Age at menarche (years)	12 ± 1.462 (Range: 8–16 years)
Menstrual Cycle Length (days)	27.95 ± 2.478 (Range: 20–38 days)
Duration of menstrual flow (days)	4.81 ± 1.116 (Range: 2–8 days)

Prevalence and severity of dysmenorrhea
Prevalence of dysmenorrhea (N = 271)	Yes	192	70.8
	No	79	29.2
Menstrual pain intensity (N = 192)	Mild	12	6.3
	Moderate	79	41.1
	Severe	101	52.6

Lifestyle/Health Characteristics (N = 192)
Exercise	Yes	77	40.1
	No	115	59.9
Smoking	Yes	1	0.5
	No	191	99.5
Chronic medical conditions associated with dysmenorrhea such as endometriosis and fibroids	Yes	5	2.6
	No	187	97.4

MHS Medicine and Health sciences, SMS Social and Management Sciences

Use of NSAIDs in dysmenorrhea and resistance

Table 3 summarizes the management of dysmenorrhea and the pattern of NSAID use among students who reported dysmenorrhea. Of the 192 students, 120 (62.5%) reported using NSAIDs such as ibuprofen, naproxen, diclofenac, or piroxicam to manage menstrual pain. Among these NSAID users, 90 students (75.0%) reported taking the recommended dosage. Despite adherence to recommended dosage, most NSAID users (83, 69.2%) reported that NSAIDs were ineffective in relieving menstrual pain., and a large proportion (98, 81.7%) perceived that NSAIDs took too long to achieve pain relief. Overall, 63 (52.5%) were classified as having NSAID-resistant dysmenorrhea which represents 32.8% of all students with dysmenorrhea (Fig. 1).

Table 3.

Management of dysmenorrhea and NSAID resistance

Question	Response	Frequency (N)	Percentage (%)
Do you use NSAIDs (e.g. Ibuprofen, naproxen, Diclofenac, Piroxicam) to manage your menstrual pain? (N = 192)	Yes	120	62.5
	No	72	37.5
Do you take the recommended dosage of NSAIDs when you have dysmenorrhea? (N = 120)	Yes	90	75.0
	No	30	25.0
Have you ever found NSAIDs to be ineffective in relieving your menstrual pain, even after taking the recommended dosage? (N = 120)	Yes	83	69.2
	No	37	30.8
Do you sometimes feel that the NSAIDs take too long before taking effect? (N = 120)	Yes	98	81.7
	No	22	18.3

Fig. 1.

Participants classified with NSAID-resistant dysmenorrhea

Management strategies and alternative therapies among NSAID-resistant students

Table 4 presents the activities undertaken and alternative medications used by students classified as having NSAID-resistant dysmenorrhea (N = 63). The most commonly reported activity was the use of alternative medications (16, 25.4%), followed by increasing the dose of NSAIDs (15, 23.8%). Other coping strategies included sleeping (11, 17.5%), visiting the hospital (11, 17.5%), and the use of heat-based therapies such as drinking hot fluids or applying heat (7, 11.1%). Some participants reported enduring the pain by crying (8, 12.7%), while fewer engaged in rest, yoga, positional changes, or increased fluid intake (4, 6.3%). With respect to alternative medications, anti-spasmodics were the most frequently used option (20, 31.7%). Herbal and complementary remedies were less commonly reported, including clove (3, 4.8%), ginger (2, 3.2%), aloe vera (1, 1.6%), and jigsimur (1, 1.6%). A small proportion of participants reported using hormonal contraceptives such as levonorgestrel (1, 1.6%) or other analgesics like paracetamol (1, 1.6%) to manage menstrual pain.

Table 4.

Activities done and Alternative medications used by NSAID-resistant participants

S/N	*Item (N = 63)	Frequency	Percent
Activities done
1	Take alternative medication	16	25.4
2	Increase dose of NSAID	15	23.8
3	Sleep	11	17.5
4	Visit the hospital	11	17.5
5	Hot water / heat therapy (drink hot water, hot water bottle, warm towel, warm fluids, heat applied)	7	11.1
6	Cry / endure pain	8	12.7
7	Rest / yoga / change position / fluids	4	6.3

Alternative medications used to manage pain
1	Anti-spasmodics	20	31.7
2	Herbal Remedies
I	Clove	3	4.8
Ii	Aloe vera	1	1.6
Iii	Jigsimur	1	1.6
Iv	Ginger	2	3.2
3	Hormonal contraceptives (levonorgestrel)	1	1.6
4	Other painkillers (paracetamol)	1	1.6

* Multiple responses

Association of demographic and menstrual characteristics with NSAID-resistant dysmenorrhea

Table 5 presents the bivariate associations between selected demographic, lifestyle, and menstrual characteristics and NSAID-resistant dysmenorrhea among NSAID users. Physical activity status was not significantly associated with NSAID resistance (χ² = 2.623, p = 0.135) while smoking or tobacco use showed no significant association with NSAID resistance (Fisher’s exact test, p = 0.475). There were no statistically significant differences between NSAID-resistant and non-resistant participants with respect to age (U = 1621.000, p = 0.352), menstrual cycle length (U = 1688.500, p = 0.549), duration of menstrual flow (U = 1744.000, p = 0.772), or age at menarche (U = 1756.000, p = 0.832).

Table 5.

Association of Demographic and Menstrual Characteristics with NSAID-Resistant Dysmenorrhea

Variables			NSAID Resistance
			Yes	No	Test statistic	p-valueabc
Physically active or engage in regular exercise	Yes		29	18	2.623	0.135a
	No		34	39
Smoke or use tobacco products	Yes		0	1	1.115	0.475b
	No		63	56
Have any chronic medical conditions (e.g. endometriosis, fibroids)	Yes		3	1	0.840	0.621b
	No		60	56
Age			Mean Rank: 57.73	Mean Rank: 63.56	1621.000	0.352c
Menstrual cycle length			Mean Rank: 58.80	Mean Rank: 62.38	1688.500	0.549c
Duration of menstrual flow			Mean Rank: 61.32	Mean Rank: 59.60	1744.000	0.772c
Age at Menarche			Mean Rank: 61.13	Mean Rank: 59.81	1756.000	0.832c
Menstrual pain score			Mean Rank: 67.79	Mean Rank: 52.44	1336.000	0.014*c
Do you sometimes feel that the NSAIDs take too long before taking effect		Yes	62	36	24.842	< 0.001*a
		No	1	21
NSAID effectiveness score			Mean Rank 46.26	Mean Rank 76.24	898.500	< 0.001*c

SD Standard deviation

^aChi-square test;^bFisher Freeman Halton Exact Test;^cMann Whitney U Test

* Statistically significant value, p<0.05

Menstrual pain score was significantly higher among students with NSAID-resistant dysmenorrhea compared with those without resistance (mean rank: 67.79 vs. 52.44; U = 1336.000, p = 0.014). In addition, perception that NSAIDs take too long to achieve pain relief was strongly associated with NSAID resistance (χ² = 24.842, p < 0.001). Effectiveness score of NSAIDS was significantly lower among NSAID-resistant participants than non-resistant participants (mean rank: 46.26 vs. 76.24; U = 898.500, p < 0.001).

Predictors of NSAID-resistant dysmenorrhea among students

Table 6 shows the predictors of NSAID-resistant dysmenorrhea among students who used NSAIDs for menstrual pain. In the unadjusted analysis, students with lower NSAID effectiveness score were significantly more likely to have NSAID resistance before (COR = 0.64, 95% CI: 0.52–0.79; p < 0.001) and after adjustment for confounders (AOR = 0.72, 95% CI: 0.57–0.90; p = 0.004).

Table 6.

Predictors of NSAID Resistance in dysmenorrhea among students

Predictor Variable	COR (95% CI)	p-value	AOR (95% CI)	p-valuea
NSAID effectiveness score	0.64 (0.52–0.79)	< 0.001*	0.72 (0.57–0.90)	0.004*
Age in years	0.94 (0.76–1.15)	0.526	0.96 (0.74–1.25)	0.768
Age at menarche in years	1.01 (0.80–1.28)	0.930	1.12 (0.83–1.50)	0.453
Menstrual cycle length in days	0.99 (0.85–1.16)	0.920	0.96 (0.78–1.17)	0.666
Duration of menstrual flow in days	1.07 (0.77–1.47)	0.693	0.94 (0.63–1.41)	0.780
NSAIDs take too long before effect (Ref: No)	36.2 (4.67–280.29)	< 0.001*	16.91 (2.0–141.6)	0.009*
Physically active (Ref: No)	1.44 (0.78–2.65)	0.242	1.34 (0.52–3.41)	0.543
Smoking (Ref: No)	–	1.000	–	1.000
Chronic medical condition (Ref: No)	3.18 (0.52–19.51)	0.212	1.97 (0.17–22.83)	0.589
Menstrual pain intensity score	1.33 (1.05–1.69)	0.018*	1.27 (0.920–1.75)	0.146

Ref  Reference value, COR Crude Odds Ratio,  AOR Adjusted Odds Ratio

^aLogistic Regression

* Statistically significant value, p<0.05

Students who reported delayed onset of NSAID action had significantly higher odds of NSAID resistance in both crude (COR = 36.2, 95% CI: 4.67–280.29; p < 0.001) and adjusted models (AOR = 16.91, 95% CI: 2.00–141.6; p = 0.009). Student who reported higher menstrual pain intensity score were more likely to have NSAID resistance dysmenorrhea than those with low scores in the crude analysis (COR = 1.33, 95% CI: 1.05–1.69; p = 0.018). However, this relationship did not remain statistically significant after adjustment (AOR = 1.27, 95% CI: 0.92–1.75; p = 0.146).

Age, age at menarche, menstrual cycle length, and duration of menstrual flow were not significant predictors of NSAID resistance in either crude or adjusted analyses. Physical activity status, smoking, and the presence of chronic medical conditions were also not significant predictors of NSAID resistant dysmenorrhea.

Discussion

This study evaluated the prevalence of NSAID-resistant dysmenorrhea, identified predictors of resistance, and explored alternative pain management strategies among female undergraduate students with dysmenorrhea. The findings reveal a significant challenge in the management of dysmenorrhea and highlight important behavioural and perceptual factors influencing dysmenorrhea management among university students.

This study found a high prevalence of NSAID-resistant dysmenorrhea among undergraduate students. Perceived delayed onset of NSAID action, and lower NSAID effectiveness scores were significant predictors of resistance. In response to ineffective NSAID therapy, students adopted diverse coping strategies, including increasing NSAID doses, using alternative medications such as antispasmodics and herbal remedies, and employing non-pharmacological measures.

In the present study, 32.8% of students who reported dysmenorrhea were classified as having NSAID-resistant dysmenorrhea, representing over half of those who used NSAIDs for menstrual pain. This prevalence is higher than figures reported in several earlier studies. Systematic reviews and clinical studies have suggested that approximately 18–25% of women experience minimal or no pain relief with NSAIDs [16, 17], while population-based data from the United States have reported perceived treatment ineffectiveness in up to 29.3–35.6% of NSAID users [20]. Nigerian studies among university students have generally reported lower rates, including 11.6% in Ibadan [18] and 4.2% in Borno State [19]. The higher prevalence observed in this study may be attributable to differences in study design, definitions of NSAID resistance, severity of menstrual pain, patterns of self-medication, or students’ perceptions of treatment effectiveness. Unlike studies that assessed general NSAID use, this study employed a more stringent classification incorporating NSAID use, recommended dosing, and persistent pain despite adherence, which may have resulted in a more accurate identification of true NSAID resistance. These findings suggest that NSAID-resistant dysmenorrhea represents a clinically relevant often under-recognized problem among undergraduate students.

Although a high proportion of NSAID users reported adherence to recommended dosages, most indicated that NSAIDs were ineffective or took too long to relieve menstrual pain. Similar findings have been reported in previous studies, suggesting that NSAID treatment failure may not be solely attributable to non-adherence but may reflect inter-individual variability in drug response, pain perception, or underlying pathophysiological mechanisms [16, 20]. These findings reinforce concerns that reliance on NSAIDs alone may be insufficient for a considerable proportion of women experiencing dysmenorrhea.

Some participants of this study employed a variety of coping strategies when NSAIDs failed to provide adequate relief, students employed a variety of coping strategies. Increasing the dose of NSAIDs was one of the most frequently reported responses. This pattern aligns with findings by Nagy and colleagues [30], who observed that individuals might resort to dose escalation when initial analgesic therapy is ineffective especially in cases of severe dysmenorrhea. While such behaviour reflects attempts to manage persistent pain, unsupervised NSAID dose escalation raises concerns regarding the risk of adverse effects, including gastrointestinal and renal complications. This underscores the importance of students’ education by pharmacists on safe analgesic use and the need for alternative, supervised treatment pathways for individuals with poor NSAID response.

The use of alternative medications was also common among students classified as having NSAID-resistant dysmenorrhea. This is in line with several studies where it has been reported that women often turn to other pharmacological options to manage menstrual pain [31, 32]. In this study, antispasmodics were the most frequently reported alternative pharmacological option. This is dissimilar to findings from a study carried out in Abuja, Nigeria where paracetamol was the most used alternative medications by the students [33]. Antispasmodics include anti-muscarinic drugs used to treat smooth muscle spasm usually indicated for reduction of uterine contraction. Its use mostly has been shown to be effective alternative taken in combination with NSAIDs or other analgesics [34].

Herbal and complementary remedies were used by a smaller proportion of participants, consistent with reports from other low- and middle-income settings where traditional medicine plays a role in menstrual pain management. Studies in Nigeria [26] and Ethiopia [35] reported majority use of herbal products by the study participants in the management of their menstrual pain. The reliance on such remedies highlights the need for culturally sensitive health education and further research into commonly used complementary therapies.

Non-pharmacological approaches, including rest, sleep, and heat-based therapies, were also reported. These strategies are documented in the literature as adjunctive or alternative methods for managing dysmenorrhea [36]. While such approaches may provide relief for some individuals, their effectiveness in cases of NSAID-resistant dysmenorrhea remains variable and insufficiently studied.

Visiting the hospital was reported by some students indicating that while some seek professional medical assistance when NSAIDs fail to provide relief, majority still rely on other methods. This aligns with other studies [37, 38] where it was reported that a lower percentage of women with dysmenorrhea sought medical attention after over-the-counter medications proved ineffective. This trend is concerning because, although there is an awareness of the need for professional care in more severe cases, many women continue to rely on other means including self-medication [39]. Not having professional care could lead to use of sub-therapeutic doses resulting to inadequate pain control. Additionally, not consulting a healthcare provider for menstrual pain can delay the diagnosis of secondary dysmenorrhea, which is often linked to conditions like endometriosis [40]. Early medical consultation is crucial to prevent the physical, emotional, and social complications associated with such conditions [41]. The lower rate in this study may reflect barriers to accessing healthcare, such as cost, availability of services, or cultural perceptions about the severity of menstrual pain. Some students reported enduring menstrual pain without taking further action. This action is consistent with findings from a systematic review across 15 countries [23] where it was reported that menstrual pain is a condition that should be endured. This behaviour may be influenced by cultural factors, a lack of awareness of alternative treatments, or the normalization of menstrual pain as something to be endured rather than treated. Studies such as that by Wiggleton-Little [42] have discussed the normalization of menstrual pain in various cultures, which can lead to underreporting and under treatment of dysmenorrhea.

Perceived delayed onset of NSAID action and lower NSAID effectiveness scores were identified as significant predictors of NSAID-resistant dysmenorrhea. Students who perceived that NSAIDs took too long to provide pain relief had markedly higher odds of resistance, suggesting that delayed analgesic onset may be an important indicator of suboptimal treatment response. This finding aligns with findings by Oladosu and colleagues [17] where it was reported that variability in pharmacokinetics, prostaglandin pathways, and pain perception may influence NSAID effectiveness. Conversely, higher NSAID effectiveness scores were associated with a lower likelihood of NSAID resistance, reinforcing the validity of patient-reported outcomes in identifying treatment response patterns. Although higher menstrual pain intensity was associated with NSAID resistance in the bivariate analysis, this relationship did not remain significant in the regression analysis, suggesting that perceived treatment effectiveness and onset of action may be more important determinants of resistance than pain severity alone.

Sociodemographic and menstrual characteristics such as age, age at menarche, menstrual cycle length, and duration of menstrual flow were not significant predictors of NSAID resistance. Similarly, lifestyle factors including physical activity, smoking, and the presence of chronic medical conditions were not associated with resistance in this study. These findings suggest that NSAID-resistant dysmenorrhea may be driven more by treatment-related and perceptual factors than by baseline demographic or menstrual characteristics in this population.

The findings of this study highlight NSAID-resistant dysmenorrhea as a substantial and clinically relevant problem among female undergraduate students. Given the widespread reliance on NSAIDs as first-line therapy, the high prevalence of treatment resistance observed underscores the need for improved screening, patient education, and access to alternative evidence-based treatments. Universities and healthcare providers should consider implementing targeted educational interventions to promote safe analgesic use, timely healthcare-seeking behaviour, and awareness of second-line treatment options for dysmenorrhea. Further research is warranted to explore the underlying mechanisms of NSAID resistance and to develop tailored management strategies for young women who do not respond adequately to standard therapy.

Strengths and limitations of study

This study provides one of the few empirical assessments of NSAID-resistant dysmenorrhea among undergraduate students in Nigeria, addressing an important and under-researched aspect of menstrual health. A key strength of the study is the explicit operational definition of NSAID resistance, which was restricted to participants who reported NSAID use, adherence to a healthcare professional–recommended dosage, and persistent menstrual pain despite such use. This approach improves the specificity and clinical relevance of the prevalence estimate compared with studies that classify resistance based solely on NSAID use or perceived inefficacy. The inclusion of delayed onset of analgesic effect as a supplementary indicator further enriched the characterization of reduced NSAID effectiveness.

However, several limitations should be acknowledged. The cross-sectional design precludes causal inferences between identified predictors and NSAID-resistant dysmenorrhea. Data were self-reported, which may be subject to recall bias, misclassification, and subjective interpretation of pain severity and treatment response. Although NSAID resistance was defined using a structured and sequential approach, it was not confirmed through objective clinical assessment, drug-specific dosing verification, or longitudinal pain measurement. Underlying gynecological conditions, such as endometriosis or uterine fibroids, were also self-reported and not clinically verified, which may have influenced perceived treatment failure. Additionally, the study was conducted in a single private university with a centralized healthcare system, which may limit the generalizability of the findings to public universities, institutions with less regulated medication access, or non-student populations. Finally, the use of a non-probability sampling approach may introduce selection bias, although proportionate allocation across colleges was employed to mitigate this.

Conclusion

NSAID-resistant dysmenorrhea is common among undergraduate students, even among those who adhere to recommended NSAID dosing. A substantial proportion of students reported inadequate pain relief and delayed onset of action, which emerged as predictors of NSAID resistance. Students adopted alternative coping strategies, including dose escalation, use of other medications, and non-pharmacological measures, some of which may pose safety concerns if undertaken without professional guidance. These findings highlight important gaps in the effectiveness of first-line dysmenorrhea management and underscore the need for improved education on appropriate NSAID use, early identification of poor responders, and timely consideration of alternative evidence-based therapies. Addressing NSAID-resistant dysmenorrhea through targeted clinical and public health interventions may improve menstrual health outcomes and quality of life among students.

Future studies and recommendations

These findings suggest that current NSAID-based treatment strategies may be insufficient for a proportion of young women, necessitating further research into alternative therapies and interventions. By addressing the specific factors contributing to NSAID resistance, healthcare providers can develop more targeted and effective strategies for managing dysmenorrhea, ultimately improving the quality of life for affected individuals. The insights gained from this study could also inform the development of educational programs aimed at enhancing the understanding and management of dysmenorrhea among young women in university settings.

Abbreviations

NSAIDs

Nonsteroidal Anti-inflammatory Drugs

ABUAD

Afe Babalola University Ado-Ekiti

ABUADHREC

Afe Babalola University Health Research and Ethics Committee

Authors' contributions

All authors contributed to the study conception and design. Material preparation, and data collection were performed by EO, IO. EA, DY, IU and PO. Data analysis was performed by EO, OF, CI. The first draft of the manuscript was written by EO, DY, PO, BA, IO, OJ, AI, and HO. IE, and IU reviewed the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Afe Babalola University Multisystem Hospital Research Ethics Committee (Date 10/12/2023/No ABUADHREC/19/12/2023/24). Electronic informed consent was obtained from all participants included in the study.

Consent for publication

Not Applicable.

Competing interests

The authors declare no competing interests.