Table 1.
Characteristics of included studies
| Citation | Study design | Location | Population | Intervention; number of participants | Comparator; number of participants |
Co-interventions | Intervention duration/ follow-up |
Outcome measures |
|---|---|---|---|---|---|---|---|---|
| Dietary supplements | ||||||||
| (Almassinokiani et al., 2016) | RCT | Iran |
Mean age 30 ± 5; Baseline VAS score (10 cm) > 3; Endometriosis stage mild-severe |
Vitamin D supplement: One oral capsule of 50 000 IU Vitamin D3 per week; n = 19 | Placebo: One oral capsule per week; n = 20 | All participants: conservative diagnostic surgery (8 weeks pre-intervention) | 12 weeks/post-intervention (EOI) |
10 cm VAS Dysmenorrhoea, non-menstrual pelvic pain Adverse events (self-report) |
| (Cobellis et al., 2011) | RCT | Italy |
Age range 24–41; Endometriosis stage I and II |
Micronized N-Palmitoylethanolamine (PEA) –transpolydatin supplement: 400 mg of PEA and 40 mg transpolydatin twice a day; n = 21 |
Placebo: One oral capsule twice a day; n = 20 Celecoxib (single course): 200 mg twice a day for 7 days; n = 20 |
All participants: conservative diagnostic surgery (pre-intervention) | 3 months/post-intervention (EOI) |
10 cm VAS Dysmenorrhoea, non-menstrual pelvic pain, dyspareunia |
| (Khodaverdi et al., 2019) | RCT | Iran |
Mean age 34 + 6; Baseline VAS score > 4; Endometriosis stage III-IV |
Lactobacilus supplement: Lactobacillus acidophilus, Lactobacillus plantarum, Lactobacillus fermentum and Lactobacillus gasseri; One capsule daily; n = 19 | Placebo: One capsule daily; n = 18 | All participants: NSAIDs if required | 8 weeks/post-intervention (EOI), 4 weeks post-intervention (ST) |
10 cm VAS Dysmenorrhoea, non-menstrual pelvic pain, dyspareunia Adverse events (self-report) |
| (Kohama et al., 2007) | Randomised comparative trial | Japan |
Mean age 33 ± 4.0; Moderate—severe pelvic pain; Endometriosis stage II-IV |
Pycnogenol supplement: French maritime pine bark extract; 30 mg twice a day via oral capsule; n = 32 | Gn-RHa therapy: Leuprorelin acetate depot; 6 × 3.75 mg every 4 weeks; n = 26 |
All participants: conservative diagnostic surgery (< 6 months pre-intervention) Intervention: continue existing therapy, analgesics as required Comparator: Add-back therapy if required (Premarin, 1.25 mg per day) |
48 weeks/post-intervention (EOI) |
NRS (0–3) Dysmenorrhoea, non-menstrual pelvic pain Adverse events (self-report) |
| (Maia et al., 2012) | Pre-post intervention study | Brazil |
Mean age 30 ± 5; Experience pain and breakthrough bleeding |
Resveratrol supplement (post-intervention): 30 mg once daily; n = 12 | OC: 3 mg drospirenone + 30ug ethinylestradiol daily (pre-intervention); n = 12 | Intervention: 3 mg drospirenone + 30ug ethinylestradiol | 6 months/2 months post-intervention (ST) |
NRS (0–3) Dysmenorrhoea |
| (Mares et al., 2020) | RCT | France |
Mean age: 34–36; Baseline VAS score (100 mm) > 40; Endometriosis stage II-IV |
Metal trace elements supplement: Oral supplement taken daily; n = 32 | Placebo: Oral capsule taken daily; n = 31 | All participants: conservative diagnostic surgery (> 6 months pre-intervention); NSAIDs if required | 120 days/post-intervention (EOI) |
100 mm VAS Pain (overall) EHP-30 QoL NSAID use (self-report) Adverse events (self-report) |
| (Mendes da Silva et al., 2017) | RCT | Brazil | Mean age 32–35 | Resveratrol supplement: 40 mg a day; n = 22 | Placebo: One oral capsule daily; n = 22 |
All participants OC: 0.15 mg levonorgestrel + 0.03 mg ethinyl estradiol |
42 days/post-intervention (EOI) |
10 cm VAS Pain (overall) Analgesic use (self-report) Adverse events (self-report) |
| (Morales-Prieto et al., 2018) | Observational case series | Germany |
Mean age 31–36; Baseline VAS score (100 mm) > 30 |
3,3'—Diindolylmethane (DIM) supplement: 100 mg three times a day for 3 months; n = 5 | OC: 2 mg dienogest once a day for 3 months; n = 5 |
All participants: conservative diagnostic surgery (pre-intervention) Intervention: 2 mg dienogest once a day for 3 months |
3 months/post-intervention (EOI) |
100 mm VAS Non-menstrual pelvic pain Analgesic use (self-report) |
| (Nodler et al., 2020) | RCT | USA |
Mean age 19–20; Baseline VAS score (10 cm) > 3 |
Vitamin D supplement: 2000 IU Vitamin D3 daily via oral capsule; n = 27 Fish oil: 1000 mg fish oil daily via oral capsule; n = 20 |
Placebo: one oral capsule daily; n = 22 | All participants: conservative diagnostic surgery (≥ 6 weeks pre-intervention); continue existing medical treatment | 6 months/post-intervention (EOI) |
10 cm VAS Pain (overall) SF-12 QoL: physical, mental Analgesic use (self-report) |
| (Schwertner et al., 2013) | RCT | Brazil |
Mean age 37–38; Baseline VAS score (10 cm) > 4; Endometriosis stage I-IV |
Melatonin supplement: 10 mg once a day via oral capsule before bed; n = 20 | Placebo: One capsule daily at bedtime; n = 20 | All participants: supplementary analgesics (acetaminophen, ibuprofen, codeine, or tramadol) if required | 8 weeks/post-intervention (EOI) |
10 cm VAS Dysmenorrhoea, dyspareunia, pain (overall) Analgesic use (self-report) |
| Dietary modifications | ||||||||
| (Marziali et al., 2012) | Retrospective observational case series | Italy |
Median age 28 years; Baseline VAS score (10 cm) > 4 |
Gluten-free diet: complete removal of ingredients derived from gluten, including those within prescription medication, vitamins, cosmetics, stabilisers, and thickening agents. Patients were educated on the diet prior to partaking; n = 295 |
Baseline (pre-intervention); n = 295 |
All participants: conservative diagnostic surgery | 12 months/post-intervention (EOI) |
10 cm VAS (0 = no pain, 1–4 = mild, 5–7 = moderate, 8–10 = severe pain) Dysmenorrhoea, non-menstrual pelvic pain, dyspareunia |
| (Sesti et al., 2007) | Randomised comparative trial | Italy |
Mean age 29–31; Endometriosis stage III–IV |
Dietary therapy dependent on BMI, physical activity, and job: vitamins (B6, A, C, E), minerals salts (calcium, magnesium, selenium, zinc, iron), VSL3 lactic ferments (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus bulgaricus, Streptococcus thermophilus), and omega-3 and omega-6 fatty acids (fish oil), secured nutritional intake between 1600—2000 cal; n = 37 |
1- Placebo; n = 115 2—Gn-RHa: either tryptorelin or leuproelin, 3.75 mg every 28 days; n = 42 3—Continous monophasic OC: 0.03 mg ethynilestradiol + 0.75 mg gestogen daily; n = 40 |
All participants: conservative laparoscopic procedure (7 days pre-intervention) | 6 months/6 months post-intervention (IT) |
10 mm VAS Dysmenorrhoea, non-menstrual pelvic pain, deep dyspareunia SF-36 QoL: Physical functioning, role limitation [physical], pain, general health perception, vitality, social functioning, role limitation [emotional], and mental health Adverse events (self-report) |
| (Signorile et al., 2018) | Non-randomised controlled trial | Italy |
Mean age 34–35; Endometriosis stage IV |
Dietary therapy 1: Two capsules daily containing 1002 mg linoleic acid (omega 3), 432 mg alpha linolenic acid (omega 3), 172.8 mg linoleic acid (omega 6), 200 mg quercetin, 20 mg nicotinamide, 400mcg 5-methyltetrahydrofolate calcium salt, 20 mg titrated turmeric, 19.5 mg titrated parthenium; n = 30 Dietary therapy 2: Two capsules daily containing linseed oil and 5-methyltetrahydrofolate calcium salt; n = 30 |
Placebo: 2 doses per day (one every 12 h); n = 30 |
All participants Diet restrictions: increase fibre 20–30%, and to increase food containing Omega 3; reduce milk and derivatives by 30%; reduce meat, gluten, caffeine, alcohol, chocolate, saturated fat, butter, and margarine by 50%; complete exclusion of soy, aloe, and oats |
3 months/post-intervention (EOI) |
10 cm VAS Dysmenorrhoea, non-menstrual pelvic pain, dyspareunia |
| OTC medication | ||||||||
| (Kauppila and Ronnberg, 1985) | Cross-over trial | Finland |
Mean age 32–35; Moderate-severe menstrual distress |
Naproxen: 2 tablets (275 mg naproxen sodium per tablet) taken orally at first sign of menstrual distress, followed by 1 tablet every 4–6 h as required; n = 11 | Placebo: 2 tablets taken orally at first sign of menstrual distress, followed by 1 tablet every 4–6 h as required; n = 9 | All participants: supplementary analgesics following two consecutive doses of study drug if required | 4 menstrual cycles (2 cycles for each comparator)/post-intervention (EOI) |
NRS (0–3) Dysmenorrhoea Analgesic use (self-report) Adverse events (self-report) |
| Exercise | ||||||||
| (Goncalves et al., 2017) | RCT | Brazil |
Mean age 35 ± 7; Baseline VAS score (10 cm) > 4 |
Hatha yoga program: 2-h session twice a week; n = 28 | No yoga: continue standard treatment (medication and/or one physiotherapy session a week); n = 12 | All participants: continue existing medical treatment | 8 weeks/post-intervention (EOI) |
10 cm VAS Pain (overall) EHP-30 QoL: Pain, control and powerlessness, emotional wellbeing, social support, self-image, work, relationship with children, sexual intercourse, doctor relationship, treatment, infertility |
BMI, body mass index; EHP-30, endometriosis health profile-30; EOI, end of intervention; Gn-RHa, gonadotropin-releasing hormone agonist; OC, oral contraceptive; NSAID, non-steroidal anti-inflammatory drug; NRS, numeric rating scale; QoL, quality of life; RCT, randomised controlled trial; SF-12, short form-12; ST, short term; USA, United States of America; VAS, visual analogue scale