Prevalence, Surgical, and Medical Management of Patients with Endometriosis amongst Indian Women

Objective: This study aims to determine the prevalence of endometriosis in women in South India, the epidemiological factors involved, and evaluate the symptomatic burden associated with it.

Design: A large-scale Hospital-based study was conducted among women of reproductive age (16 to 44 years) in the state of Telangana between March 2018 and March 2023. A randomized multi-stage stratified sampling method was adopted and included 2,400 women who were screened using a validated structured questionnaire. Patients presenting with symptoms indicative of endometriosis underwent additional assessment using abdominal ultrasonography (AUS) and serum cancer antigen 125 (CA125) tests. For confirmation, laparoscopy was offered to the patients who consented. Patients who declined laparoscopy were given the option of undergoing magnetic resonance imaging (MRI) instead.

Results: Among 2,400 women who participated, 60 women have been diagnosed with endometriosis during the 5-year study period. The prevalence of endometriosis was found to be 2.5%. The mean age of participants was 15.2 ± 3.5 years and the mean age at menarche was found to be 12.9 ± 1.1 years. Out of 60 participants diagnosed with endometriosis 30% (n = 18) experienced irregular menstrual cycles. Approximately 33.3% (n = 20) of the women reported experiencing Dysmenorrhea, with 28.4% (n = 17) complaining of dyspareunia. Among the cases with menstrual pain, exhibited ultrasound findings suggestive of endometriosis, with elevated CA125 levels observed in 45% (n = 27) of these cases. All 60 patients who consented to laparoscopic confirmation, exhibited positive histo-pathological evidence of endometriosis. The prevalence of endometriosis is found to be significant in women of reproductive age group and found to be associated with high rates of infertility in 15 (25%) patients. The results of this study showed that the prevalence of endometriosis is found to be 2.5% which is similar to the other studies reported. The severity of endometriosis during laparoscopy was assessed using the rAFS staging system, revealing rates of 55% and 45% for disease in Stages I & II, Stages III, & IV, respectively.

Conclusion: Our study concludes that endometriosis predominantly affects women in the reproductive age group and is often associated with primary infertility. The laparoscopic findings are identified as a standard tool for both diagnosis and treatment of endometriosis.

Introduction

Endometriosis is a complex, multifactorial, gynecological debilitating disease characterized by an endometrial-like tissue present outside of the uterus. It is an estrogen-dependent very complex chronic inflammatory process that affects primarily reproductive-aged women in the pelvic tissues, including the ovaries.

The increasing prevalence of Endometriosis is a global concern, with variations observed across different regions, countries, and ethnicities. The prevalence of endometriosis among women worldwide ranges from 6–10 percent. It affects ∼247 million women globally and ∼42 million women in India [1]. It causes dysmenorrhea, chronic pelvic pain, dyspareunia, dyschezia, fatigue, depression, cyclic urinary and intestinal symptoms and infertility, resulting in significant socioeconomic impact [2].

Endometriosis primarily presents itself between menarche and menopause, although instances of the disease have been documented in pre-menarcheal girls and post-menopausal women. The etiology of endometriosis is unclear. Endometriosis is associated with various pathogenic theories, such as Sampson’s spill theory, Meyer’s metaplastic theory, Halban’s Lymphovascular theory, and the Immunological theory, with the latter gaining significant prominence [3], [4].

Estimating the incidence proves challenging due to the asymptomatic nature of the disease and the utilization of imaging techniques that exhibit low sensitivity in diagnosis.

Some possible risk factors for endometriosis include an early age at menarche, shorter menstrual cycle length, frequent menstrual cycles, infertility, low parity, Mullerian anomalies, and a history of endometriosis in a first-degree relative [5], [6]. The study aimed to investigate the prevalence and other epidemiological factors within the population of South India, with additional efforts made to establish correlations between clinical diagnoses and histopathological outcomes.

Often endometriosis treatment is according to a woman’s symptoms, preferences, and priorities rather than the stage of endometriosis. For endometriosis treatment, Laparoscopy is the gold standard, but recurrence rates are high, and symptoms remain unresolved most of the time. It is also affected by the extent of the disease staging [7]–[9].

Methodology

The study received ethical approval from the Institutional Review Board for Bioethics at MHRI Hospital, Hyderabad, prior to commencement. Each patient provided informed consent after a thorough explanation of the research and its objectives. Inclusion in the study was contingent upon the signing of the informed consent form. Researchers upheld patient data confidentiality and adhered to the principles outlined in the declaration.

Study Setting and Design

It is a retrospective-prospective cross-sectional hospital-based study carried out at MHRI Hospital and Research Centre as it is a Tertiary care center. from the March 2018 to March 2023.

Inclusion Criteria: The study included women aged 16–44 years with primary or secondary infertility who underwent diagnostic hystero-laparoscopy and chromopertubation tests and were diagnosed with endometriosis.

Exclusion Criteria: Women with pelvic inflammatory disease (PID), adhesions resulting from prior surgeries, or infections were not included in the study.

The study sample encompassed all patients exhibiting clinical features suggestive of endometriosis who has visited the Gynaecology Outpatient Department and met the specified inclusion criteria. By purposive sampling, the total women who fulfilled inclusion criteria and consented for study were taken. Comprehensive histories were obtained from the patients, covering prior treatments, personal details, family background, obstetric history, and epidemiological details. Detailed clinical examinations were conducted, and relevant investigations were carried out. The diagnostic approach for endometriosis was classified as non-invasive (clinical examination, imaging techniques) or invasive (laparoscopy or laparotomy).

Clinical Characteristics: Noted points included the patients’ age, type and duration of infertility, menstrual cycle details such as frequency and flow, and the presence of symptoms such as dysmenorrhea, dyspareunia, chronic pelvic pain, and urinary symptoms, along with their correlation to the stage of endometriosis. Physical Examination: Analysis focused on the presence of abdominal or adnexal masses, the mobility of the uterus, and the presence of adnexal tenderness.

During laparoscopy/laparotomy, lesion characteristics were documented, and biopsies were performed for histopathological analysis. Noted endometriotic lesions varied in color, including dark blue, powder-burn black, red, white, yellow, brown, or non-pigmented lesions. The size, depth, and location of these lesions were observed to determine the severity of endometriosis. The laparoscopic staging was based on the revised American Fertility Society (AFS) scoring, which classified findings into four stages [10].

Stage I (Minimal): Characterized by a few endometrial implants, often in the Cul-de-sac.

Stage II (Mild): Involves endometrial implants affecting one or both ovaries.

Stage III (Moderate): Indicates moderate levels of endometriosis with implants in several reproductive areas and in one or both ovaries.

Stage IV (Severe): Indicates widespread endometriosis implants throughout the pelvic area (Fig. 1).

Fig. 1. Clinical different stages of endometriosis diagnosed by laparoscopy: A) Stage I (Minimal), B) Stage II (Mild), C) Stage III (Moderate), D) Stage IV (Severe).

Results

During the five years of study period, 2,400 women were examined, of whom 60 were diagnosed to have Endometriosis. 33 of Stage I and Stage II Endometriosis, 27 of Stages III & IV Endometriosis (Fig. 2). The demographic and clinical characteristics of the participants with Endometriosis are summarized and the indications for their visit in Table I clinical characteristics of women with endometriosis, including the distribution of presenting symptoms within a sample of symptomatic women diagnosed with endometriosis for the first time, categorized by age groups in Fig. 3.

Fig. 2. Flow chart illustrates the subjects recruited for a hospital-based study.

Table I. Illustrates Socio-Demographic Characteristics of Women with Endometriosis

Characteristics	Variables	Women with endometriosis(n = 60)	Women without endometriosis(n = 2340)
Age (year)	16–24 years	14 (23.3%)	–
	25–34 years	24 (40%)	–
	35–39 years	16 (26.7%)	–
	40–44 years	6 (10%)	–
	Age at menarche	12.87 ± 1.13	12.56 ± 1.13
	Height (cm)	148.47 ± 7.17	149.95 ± 10.93
	Weight (kg)	52.07 ± 12.71	55.71 ± 12.93
	BMI (kg/m2)	55.71 ± 12.93	55.71 ± 12.93
Menstrual cycles	Regular cycles	42 (706%)
	Irregular cycles	18 (30%)
Marital status	Married	36 (60%)	2080 (88%)
	In relationship	2 (3.3%)	16 (0.68%)
	Unmarried	18 (30%)	216 (9.2%)
	Separated/divorced	1 (1.6%)	15 (0.64%)
	Widow	3 (5%)	13 (0.5%)
Education level	Primary	4 (6.7%)	58 (2.4%)
	High School	10 (16.7%)	72 (3%)
	Higher education	46 (76.6%)	2210 (94.4%)
Employment	Not employed	3 (5%)	141 (6%)
	Paid work, full time	32 (53.3%)	1118 (47.8)
	Paid work, part time	6 (10)	268 (11.4)
	Housewife	8 (13.3)	348 (15)
	Student	11 (18.4)	465 (19.8)
Type of infertility	Primary infertility	40 (75%)	-
	Secondary infertility	20 (25%)

Fig. 3. The frequency of endometriosis according to patient age at the time of diagnosis of endometriosis.

Out of the 60 patients studied, 40 (75%) were diagnosed with primary infertility, while 20 (25 %) had secondary infertility. The average age of the patients was 29 ± 4.3 years (Range: 16-44 years). Among the patients, the most common complaints, apart from infertility, were dysmenorrhea 21 (35%), followed dyspareunia 17 (28.4%), abnormal uterine bleeding 7 (11%) and infertility 15 (25%) depicted in Fig. 4. Interestingly, over 50% of cases were asymptomatic. The study found a statistically significant association between adnexal tenderness and restricted uterine mobility with the staging of the disease (p < 0.01). Abnormal ultrasound (USG) findings were observed in 28 (46.6%) of cases, with the presence of cysts or endometriomas cases. This finding was clinically significant, as sonograpically detected endometriomas were confirmed laparoscopically summarized in Table II.

Fig. 4. The clinical characteristics of endometriosis according to the age group.

Table II. The Clinical Characteristics of Women with Endometriosis, Including the Distribution of Presenting Symptoms within a Sample of Symptomatic Women Diagnosed with Endometriosis for the First Time, Categorized by Age Groups.

Characteristics	16–24 years (14)	25–34 years (24)	35–39 years (16)	40–44 years (6)	Total (60)
Dysmenorrhea	7 (50%)	8 (33.3%)	4 (25%)	2 (33.3%)	21 (35%)
Dyspareunia	4 (28.6%)	7 (29.1%)	3 (18.7%)	3 (50%)	17 (28.4%)
Abnormal uterine bleeding	0	4 (16.6%)	2 (12.5%)	1 (16.7)	7 (11.6%)
Infertility	3 (21.4%)	5 (21%)	7 (43.7%)	0	15 (25%)
Diagnostic method by USG chocolate Cyst	11 (78.5%)	3 (12.5%)	2 (12.5%)	0	16 (9.6%)
USG by adenomyosis	0	1 (4.1%)	6 (37.5%)	5 (83.3%)	12 (7.2%)

All 27 (45%) cases of Stages III & IV endometriosis in the study had endometriomas in one or both ovaries. According to the Revised American Fertility Society (AFS) score (1985), Stages I & II endometriosis was found in 33 patients (55%) as depicted in Table III. The study also demonstrated a clear correlation between USG and laparoscopic evidence of endometriosis with the stage of the disease.

Table III. The Correlation between Age of Women with Endometriosis and Disease Stages

Endometriosis staging by laparoscopy	16–24 years (14)	25–34 years (24)	35–39 years (16)	40–44 years (6)	Total (60)
Stage I & II (Minimal and mild form)	12 (86%)	18 (75%)	1 (6.25%)	2 (33.3%)	33 (55%)
Stage III & IV (Moderate and severe form)	2 (14%)	6 (25%)	15 (93.75)	4 (66.7%)	27 (45%)

Investigation

In the realm of investigations, a preoperative ultrasound was conducted for all patients. Among the remaining 60 patients with positive ultrasound results suggestive of endometriosis with 33 (55%) patients were having Stage I & II (Minimal and Mild form) of endometriosis and 27 (45%) patients were having Stage III & IV (Moderate and Severe form) of Endometriosis.

Furthermore, CA 125 levels were assessed in 27 patients of Stage III and Stage IV, with (45%) displaying elevated levels (>35.0 IU/mL). The average CA 125 level among these patients was 104.1 IU/mL, ranging from 14 to 839.5 IU/Ml.

Medical Management

Prior to the laparoscopy procedure, 60 patients were administered medical treatment, which included combined oral contraceptive pills for chocolate cysts- 27 patients (45%), progestogens for adenomyosis 12 patients (20%), Dienogest for 18 patients (30%) and GnRH agonists for 3 patients (5%) as shown in Table IV.

Table IV. Medical Management of Endometriosis

Treatment received prior to laparoscopy
Treatment type	No of patients (n = 60)
OCPs for chocolate cysts	27 (45%)
GnRH agonist	3 (5%)
Dienogest	18 (30%)
Progesterone for adenomyosis	12 (20%)

Surgical procedures were primarily conducted laparoscopically for all 60 patients (100%) who ultimately necessitated a laparotomy due to the presence of large cysts. The severity of endometriosis was categorized based on the Revised American Society for Reproductive Medicine classification, revealing that 33 patients (55%) had Stages I and II mild form of disease and Stages III and IV disease, 27 (45%) had disease.

Following the operation, 27 patients (45%) were prescribed the combined oral contraceptive pill, 12 patients (20%) were put on progestogens, 18 (30%) patients were given Dienogest and 3 (5%) patients were given GnRH agonist. The follow-up duration varied from 1 week to 4 years, with 60 patients failing to adhere to the follow-up schedule.

Discussion

Endometriosis continues to be an enigmatic disorder without a definitive cure, characterized by distinctive immunological changes. It is primarily prevalent among individuals in the reproductive age group often leading to primary infertility. Predicting the stages of endometriosis in correlation with the age of affected women remains challenging. In this particular study, the mean age was determined to be 15.2 ± 3.53. Other studies have reported similar findings, with mean ages of 14–20 and 15–21 years respectively [11], [12].

The prevalence of endometriosis has notably increased significantly impacting quality of life. Despite the advent of numerous recent technological advancements, diagnosing and managing this condition continues to pose significant challenges. This hospital-based study revealed that, when the at-risk population is 25 to 34 years. The highest incidence of clinically diagnosed endometriosis was observed among women aged 25 to 34 years followed by 35 to 39 years.

Endometriosis primarily presents itself between menarche and menopause, although instances of the disease have been documented in pre-menarcheal girls and post-menopausal women. Endometriosis is prevalent in one out of every three women with infertility, 70% of women experiencing unexplained infertility, 30% of adolescent girls with secondary dysmenorrhea, 60% of women suffering from chronic pelvic pain, and 30% of women diagnosed with adenomyosis [13], [14].

Within Canada and the United States, the incidence of endometriosis spans from 5 to 15% among women of reproductive age and from 2 to 5% among postmenopausal women [15]–[18].

Estimating the incidence proves challenging due to the asymptomatic nature of the disease and the utilization of imaging techniques that exhibit low sensitivity in diagnosis. In order to manage endometriosis effectively, there needs to be individualized treatment that takes into account the entire clinical problem, including the effects of the disease and the treatment on quality of life (QoL) [19], [20].

The primary symptoms of endometriosis encompass dysmenorrhea, chronic pelvic pain, infertility, dyspareunia, as well as cyclic urinary and intestinal symptoms.

The prevalence rates identified in our research is 2.5% align with those reported in earlier cohort studies. Other studies have found prevalence rates of 2% (including diagnoses of endometriosis and adenomyosis) in Italy [21] 1.9% in the United States, [22] 1.5% in the United Kingdom, [23] 1.5% in hospitalized women of childbearing age in France, [24], 1.08% in Israel, [25] 0.1% in Germany, [26] and 2.12–3.56 per 1000 women in South Korea [27]. Another Research study from Israel reported that there was an annual increase of 1.6% in incident endometriosis cases between 2000 and 2015.

The study is characterized by various strengths and limitations. A notable strength is the utilization of large, representative, well defined diagnostic criteria, substantial consecutive sample size and unbiased group of women, enabling precise estimates within a population-based cohort in South India. Additionally, all consultations and examinations were conducted by a single examiner with extensive experience in gynecological ultrasound. This approach facilitated consistent data collection and ultrasound examinations, thereby reducing inter observer variability.

Conclusion

Endometriosis has the potential to induce severe disease in both adolescents and young females. It significantly impacts women in their reproductive years, often resulting in primary infertility. Predicting the stages of endometriosis in correlation to the age of affected women proves challenging. Initiating treatment at an earlier stage may help prevent damage to the ovaries and adjacent structures, decrease the likelihood of adhesions, and consequently mitigate the impact on fertility.