Table 11Key outcomes of hormonal therapies for noncyclic CPP

Author, Year, Country
Intervention, N at Enrollment (N at Followup)Last Outcome Assessment Post Treatment Day 1Key Findings
Vercellini et al., 2010,97 Italy
Quality: Poor
G1: Vaginal ring (15 mcg ethinyl E and 120 mcg etonogestrel/day), 72 (32)
G2: Transdermal patch (20 mcg ethinyl E and 150 mcg norelgestromin/day), 23 (19)
At end of 12 months of treatment
  • Pain symptoms reduced significantly in both groups, with no significant difference between groups
  • No differences in pain outcomes in those with or without rectovaginal lesions. Patients who chose patch were more likely to drop out of the study compared with those who chose ring (RR, 1.7; 95% CI, 1.27 to 2.28)
  • Irregular bleeding was a common side effect in both groups in those who attempted continuous use (ring 46%, patch 42%)
  • Ring users were more likely to be satisfied with treatment
Stratton et al., 2008,77 US
Quality: Good
G1: Raloxifene, 180 mg/day, 47 (38)
G2: Placebo, 46 (35)
12 months after patient completed 6 months of treatment
  • Raloxifene group experienced quicker return of pain (p=0.03) and required repeat surgery sooner than placebo group (p=0.016)
  • Presence of biopsy-proven endometriosis was not significantly associated with return of pain
  • Study terminated early due to negative effect
Zupi, et al., 2004,98 Italy

Quality: Poor
G1: GnRH-analogue (leuprolide acetate 11.25 mg IM every 3 months), 46 (NR)
G2: GnRH-analogue (leuprolide acetate 11.25 mg IM every 3 months) and transdermal E2 25 mcg/day + norethindrone 5 mg/day, 44 (NR)
G3: Estroprogestin alone (ethinyl E2 30 mcg/day + gestodene 0.75 mg/day), 43 (NR)
6 months after patient completed 12 months of treatment
  • Patients treated with GnRH-analogue (either with or without add-back therapy) had significantly greater reduction in pain scores compared with those treated with oral contraceptive therapy (p<0.01)
  • Significant loss of bone mineral density noted in both GnRH-analogue groups, but less so in the group given add-back therapy
  • Patients treated with GnRH-analogue plus add-back therapy reported overall better quality of life than those in the other 2 groups
Parazzini et al., 2000100 Italy
Quality: Poor
G1: Estroprogestin (gestodene/ethinyl estradiol) 0.75 mg/0.03 mg daily for 12 months, 46 (NR)

G2: GnRH agonist (triptorelin) 3.75 mg IM for 4 months, followed by estroprogestin daily for 8 months, 49 (NR)
12 months
  • Significant improvement in pain scores over 12 months of treatment in both groups
  • No statistically significant difference between groups in overall pain improvement
  • Endometriosis stage had no significant effect on pain status
Ling et al., 1999,81 US

Quality: Fair
G1: Depot leuprolide, 3.75 mg IM every 4 weeks, 50 (49)
G2: Placebo, 50 (46)
At end of 12 weeks of treatment
  • Leuprolide group had significant reduction in all pain scores compared with placebo (p<0.001)
  • Majority of patients in both groups had laparoscopically-confirmed endometriosis after 12 weeks of treatment (leuprolide 78%, placebo 87%)
  • Most commonly-reported statistically significant harms in the treatment group were hot flushes (80%), insomnia (40%), and enlarged abdomen (percentage not reported) (p ≤ 0.50)
Gestrinone Italian Study Group, 1996,83 Italy

Quality: Poor
G1: Gestrinone, 2.5 mg/2× week, 27 (17)
G2: Leuprolide acetate, 3.75 mg IM every 4 weeks, 28 (17)
6 months after patient completed 6 months of treatment
  • Both groups experienced significant reduction in pain during the treatment period
  • Gestrinone group showed overall lower pain scores at the end of followup, compared with the leuprolide group
  • Recurrence of moderate-severe pain observed less frequently in the gestrinone group, compared with the leuprolide group (OR, 0.12; 95% CI, 0.02 to 0.69)
  • Nonsignificant increase in bone mineral density in the gestrinone group and a statistically significant decrease (-3.04% ± 4.77%) in the leuprolide group
Vercellini et al., 1996,99 Italy

Quality: Poor
G1: Depot medroxy-progesterone acetate, 150 mg IM every 90 days, 36 (36)
G2: Monophasic OCPs (ethinyl estradiol 0.02 mg/desogestrel 0.15 mg) with danazol 50 mg), 32 (32)
At the end of 12 months of treatment.
  • Significant improvements in pain scores noted in both treatment groups without significant between-group difference
  • 72.5% of depot medroxyprogesterone patients were either satisfied or very satisfied with treatment, compared with 57.5% of OCP users
  • Larger proportion of depot medroxyprogesterone patients experienced side effects during the treatment period
Vercellini et al., 1993,82 Italy

Quality: Poor
G1: Goserelin, 3.6 mg every 28 days, 29 (26)
G2: Monophasic OCP with ethinyl estradiol 0.02 mg/day, 28 (24)
6 months after patient completed 6 months of treatment
  • Both groups experienced improvement in pain during treatment without significant differences between groups
  • At end of followup, both groups experienced similar return to baseline pain levels
  • Symptoms recurred in most patients 6 months after treatment end
Walton et al., 1992,103 UK

Quality: Poo
G1: Medroxyprogesterone acetate, 50 mg/day for 4 mos, 107 (68)
G2: Placebo, 58 (33)
At the end of 4 months of treatment
  • 30/68 G1 participants and 9/34 G2 participants experienced 50% reduction in pain scores (100mm VAS)
  • No statistically significant between group differences
  • Discontinuation reasons included noncompliance, pregnancy, adverse events, and lack of efficacy

Abbreviations: CI = confidence interval; CPP = noncyclic chronic pelvic pain; G = group; GnRH = gonadotropin releasing hormone; IM = by mouth; mg = milligram; OCP = oral contraceptive pills; OR = odds ratio; N = number; NR = not reported; RR = relative risk.

From: Results

Cover of Noncyclic Chronic Pelvic Pain Therapies for Women: Comparative Effectiveness
Noncyclic Chronic Pelvic Pain Therapies for Women: Comparative Effectiveness [Internet].
Comparative Effectiveness Reviews, No. 41.
Andrews J, Yunker A, Reynolds WS, et al.

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