An assessment of the efficacy and safety of dydrogesterone in women with ovarian endometrioma: An open‐label multicenter clinical study

Abstract

Purpose To assess the efficacy and safety of dydrogesterone in Japanese women with ovarian endometrioma in a real‐world setting. Methods The post‐marketing study involved 15 sites in Japan. Dydrogesterone 10 mg twice daily orally was administered for 21 days (day 5‐25 of each menstrual cycle) for 4 cycles. The primary outcome measure was the change in ovarian endometrioma volume from baseline. Secondary outcome measures included total dysmenorrhea score (0 = absent to 3 = severe), severity of dysmenorrhea pain [0‐10cm visual analog scale (VAS)], serum carbohydrate antigen 125 (CA‐125) levels, and safety. Results The study group comprised women with an endometrioma aged 20 to 49 (47.4% cases aged ≥40 years). Endometrioma volume was reduced in 50% (26/52), unchanged in 25% (13/52), and increased in 25% (13/52) of women from baseline to the end of cycle 5; three‐quarters of patients thus had either reduced or unchanged ovarian endometrioma volume. Dydrogesterone significantly reduced total dysmenorrhea scores and severity of dysmenorrhea pain VAS during treatment compared with baseline. CA‐125 levels were not significantly changed during the study. The incidence of adverse events and adverse drug reactions in 59 subjects was 13.6% and 11.9%. Conclusions Dydrogesterone prevented an increase in endometrioma size in many women, and it also significantly improved total dysmenorrhea scores and severity of dysmenorrhea pain, and was well tolerated. The ClinicalTrials.gov identifier of the study was NCT02921763.

Medical Management of Ovarian Endometriomas

“…Twenty-three studies had cyst size change as a primary outcome, only four of which included a sample size calculation powered to detect change in size. 15,17,22,35…”

“…Among these, 32 studies were excluded for the following reasons: abstract only or conference proceeding (n520), absence of extractable data (n55), full text not available (n54), ineligible setting (n52), absent outcome of interest (n51). The remaining full-text articles included in this systematic review originated from Italy, [7][8][9][10][11][12][13][14][15][16][17][18] Japan, [19][20][21][22][23][24][25][26][27][28][29] Turkey, 4,30,31 the United States, [32][33][34] India, 35 Thailand, 36 Denmark, 37 and the United Arab Emirates. 38 See Figure 1 for the PRISMA flow diagram.…”

“…Twenty-three studies had cyst size change as a primary outcome, only four of which included a sample size calculation powered to detect change in size. 15,17,22,35 Diagnosis of endometrioma was most commonly performed with ultrasonography; however, four studies used MRI either in conjunction with ultrasonography or in place of it. Mean follow-up ranged from 8 weeks to 72 weeks (median 24 weeks).…”

Dydrogesterone as an Option in the Medical Treatment of Endometriosis: A Brief Comment

“…10 Following the same reasoning, the ability of dydrogesterone to prevent the increase in size of ovarian endometriomas must be reassured by robust studies. 11 It is true that the absence of clinically relevant activity on estrogen, glucocorticoid, mineralocorticoid, or androgenic receptors may be a positive characteristic of dydrogesterone in currently recommended daily doses versus other progestagens. In addition to favoring the lower occurrence of adverse events, that pharmacological profile may be safer for women in childbearing age, in the absence of contraception.…”

Analysis of Adverse Events and Medical Errors in Long-Term Hormone Treatments for Endometriosis: A Study Based on the US Food and Drug Administration Event Reporting System

“…There have been some real-world studies focusing on specific drugs for endometriosis, but they either produced negative result or concentrated on drug efficacy. [15][16][17] Pharmacovigilance evidence determining adverse reactions of long-term hormone drugs for endometriosis are still inadequate.…”