Safety and tolerability of dienogest in endometriosis: pooled analysis from the European clinical study program
Open accessAbstract
BACKGROUND: In four randomized, controlled, European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity in endometriosis. We describe a pooled analysis of the safety and tolerability data from these trials to confirm and further characterize the safety profile of dienogest in the treatment of endometriosis. METHODS: All 332 women treated with dienogest 2 mg who participated in the four clinical trials were included in the pooled analyses for safety assessments, including adverse events, laboratory tests, vital signs, body weight, and bleeding patterns. Safety variables were analyzed using descriptive statistics. RESULTS: Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis. The most common adverse drug reactions were headache, breast discomfort, depressed mood, and acne, each occurring in <10% of women. All these adverse events were generally of mild-to-moderate intensity and associated with low discontinuation rates. The bleeding pattern associated with dienogest 2 mg was well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation. Laboratory and vital sign assessments indicated no safety concerns for dienogest. Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency. CONCLUSION: In this pooled analysis of 332 women with endometriosis, dienogest was well tolerated with a favorable safety profile extending over a period of up to 65 weeks. There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis. These pooled analyses from four clinical trials of dienogest 2 mg represent a contribution to evidence-based medicine in endometriosis, providing outcomes of potential relevance to daily practice.
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Written from the paper’s full text.
TL;DR
This pooled analysis of 332 women with endometriosis treated with dienogest 2 mg once daily across four European trials found a favorable safety and tolerability profile over treatment periods up to 65 weeks. Adverse drug reactions were mostly mild-to-moderate, with headache, breast discomfort, depressed mood, and acne each occurring in <10% of women.
Key findings
- In the pooled dienogest 2 mg group (n=332; mean treatment duration 39.8 weeks), 89.2% completed the planned study durations, including 90.5% in the long-term extension study; only one woman (0.3%) discontinued for lack of efficacy.
- The most common adverse drug reactions were headache (9.0%), breast discomfort (5.4%; 18 women), depressed mood, and acne, each in <10% of women; hypoestrogenic adverse drug reactions were uncommon: vulvovaginal dryness 0.6%, loss of libido 1.5%, and hot flushes 2.7%.
- In total, 18 adverse events in 15 women (4.5%) led to study discontinuation, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation; 12 serious adverse events occurred in 11 women, with three rated by investigators as “probably related” or “possibly related” (two depression, one ovarian cyst).
- Laboratory and vital sign assessments showed no safety concerns; mean estradiol did not change substantially over up to 65 weeks, whereas leuprolide acetate decreased mean estradiol from 299.0 pmol/L to 68.5 pmol/L at 24 weeks, and lumbar spine BMD changed by +0.25% with dienogest versus −4.04% with leuprolide acetate at 24 weeks.
Methods
- Pooled safety analysis of four randomized, controlled European trials; of 514 women with confirmed endometriosis, 332 were treated with dienogest 2 mg once daily for 12 to 65 weeks, and the full analysis set included women who took study medication at least once with at least one post-baseline observation.
- Safety assessments included adverse events/adverse drug reactions, laboratory tests, vital signs, body weight, gynecologic examination, cervical smear, breast examination, bone metabolism/BMD in a subgroup, and bleeding diaries; bleeding was analyzed in 90-day WHO reference periods.
- All safety variables were analyzed descriptively (means, standard deviations, quartiles, frequencies) using SAS Version 9.2.
Limitations
- Paper-stated: gynecologic examination findings could not be meaningfully pooled because documentation differed across the individual studies.
- Paper-stated: bleeding data showed large interindividual variability, and estradiol data could not be directly compared with a pharmacodynamic trial in healthy women because of methodological differences.
- Evident from the text: safety outcomes are descriptive only, with no formal between-group statistical testing in the pooled analysis, and the pooled dienogest population comes from trials with differing designs, comparators, and treatment durations.
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Claims the paper makes
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- Findingcitation
Of 514 women with confirmed endometriosis included in the four studies, 332 were treated with dienogest 2 mg once daily for study periods between 12 weeks and 65 weeks.
“Of 514 women with confirmed endometriosis who were included in the four studies, 332 were treated with dienogest 2 mg once daily for study periods between 12 weeks and 65 weeks.10–13”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
- Findingown data
Dienogest 2 mg is well tolerated with a favorable safety profile extending over up to 65 weeks in women with endometriosis.
“Pooled analyses of this large patient population confirmed that dienogest 2 mg is well tolerated, with a favorable safety profile extending over a period up to 65 weeks in women with endometriosis.”
Quote in the paperSubstantial claim- Rests on an assumption: The four trials together included women who are representative of the wider population of endometriosis patients.
- Findingown data
The adverse events associated with dienogest 2 mg were associated with low discontinuation rates.
“AEs in the pooled population treated with dienogest 2 mg were generally mild or moderate in intensity and were associated with low premature discontinuation rates.”
Quote in the paperSubstantial claim - Findingown data
The most common adverse drug reactions in the pooled dienogest 2 mg population were headache, breast discomfort, depressed mood, and acne.
“Consistent with the four individual studies, the most common ADRs in the pooled population treated with dienogest 2 mg were headache, breast discomfort, depressed mood, and acne (Table 3).”
Quote in the paperSubstantial claim - Findingown data
Only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation.
“The bleeding pattern associated with dienogest 2 mg was generally well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation (diary data on bleeding patterns are described).”
Quote in the paperSubstantial claim
- Findingown data
Estradiol levels in women treated with dienogest 2 mg were maintained within the low-physiological range.
“Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency.”
Quote in the paperSubstantial claim - Findingown data
The adverse events associated with dienogest 2 mg were generally of mild-to-moderate intensity.
“AEs in the pooled population treated with dienogest 2 mg were generally mild or moderate in intensity and were associated with low premature discontinuation rates.”
Quote in the paperSubstantial claim - Findingown data
The full analysis set for the pooled assessments included 332 women treated with dienogest 2 mg once daily for a mean duration of 39.8 weeks.
“The full analysis set for the pooled assessments included 332 women who were treated with dienogest 2 mg once daily for a mean duration of 39.8 weeks.”
Quote in the paperNot a substantial claim - Findingreasoning
The remaining SAEs were considered unlikely to be related to study medication by the respective investigators.
“Based on the characteristics of the events and the conditions of their occurrence, the remaining SAEs (ie, breast cancer, cholelithiasis, chronic sinusitis, hospitalized because of pelvic pain, hospitalized because of abdominal pain, kidney calculus/renal colic [two events in one patient], and planned hysterectomy) were considered unlikely to be related to the study medication by the respective”
Quote in the paperNot a substantial claim - Findingcitation
Dienogest 2 mg was associated with minimal changes in bone turnover markers and lumbar spine BMD at 24 weeks.
“As previously reported, dienogest 2 mg was associated with minimal changes in bone turnover markers (bone alkaline phosphatase, osteocalcin, and urinary CrossLaps) and in lumbar spine BMD at 24 weeks.12”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- Findingown data
Individual occurrences of abnormal vital signs were rare in all studies.
“Individual occurrences of abnormal vital signs were rare in all studies.”
Quote in the paperSubstantial claim - Findingown data
No further increase in body weight was observed in the patient group treated with dienogest 2 mg for longer than 24 weeks.
“No further increase was observed in the patient group treated with dienogest 2 mg for longer than 24 weeks (Figure 1).”
Quote in the paperNot a substantial claim - Findingown data
Breast discomfort was reported in 18 (5.4%) women treated with dienogest 2 mg.
“Breast discomfort was reported in 18 (5.4%) women treated with dienogest 2 mg, including the reported terms: breast tenderness (n=11), breast engorgement (n=4), and breast pain (n=3).”
Quote in the paperNot a substantial claim - Findingown data
No individual AE was responsible for increased premature discontinuation in more than 1% (more than three women) in the dienogest 2 mg group.
“No individual AE was responsible for increased premature discontinuation in more than 1% (ie, in more than three women) in the dienogest 2 mg group.”
Quote in the paperSubstantial claim - Findingown data
Three women had SAEs that investigators rated as probably or possibly related to study medication (two cases of depression and one case of ovarian cyst).
“Three women had SAEs that the investigators rated as “probably related” or “possibly related” to the study medication (two cases of depression and one case of ovarian cyst).”
Quote in the paperNot a substantial claim - Findingown data
Lack of efficacy was reported by only one woman (0.3%) in the pooled population as the reason for premature discontinuation.
“Lack of efficacy was reported by only one woman (0.3%) in the pooled population as the reason for premature discontinuation.”
Quote in the paperNot a substantial claim - Findingown data
The number of discontinuations due to heavy or irregular bleeding was low (2 of 332 women).
“Notably, the number of discontinuations due to heavy or irregular bleeding was low (ie, 2 of 332 women), indicating that dienogest 2 mg is well tolerated by women in light of its efficacy for pain relief.”
Quote in the paperSubstantial claim - Findingown data
The standard deviations in Table 5 indicate a large interindividual variability in the number and duration of bleeding episodes in women treated with dienogest 2 mg.
“The sizes of the standard deviations in Table 5 indicate a large interindividual variability in the number and duration of bleeding episodes in women treated with dienogest 2 mg.”
Quote in the paperNot a substantial claim - Findingown data
Of 276 women treated with dienogest 2 mg who had normal baseline smear results, three (1.1%) had an abnormal smear result at end of treatment, considered unlikely related to treatment.
“Of 276 women treated with dienogest 2 mg who had normal results for smear assessment at baseline, three women (1.1%) had an abnormal smear result at the end of treatment, which in each case was considered unlikely to be related to treatment.”
Quote in the paperNot a substantial claim - Findingown data
Mean estradiol levels in the pooled dienogest 2 mg group did not change substantially during treatment up to 65 weeks.
“Mean estradiol levels in the pooled dienogest 2 mg group did not change substantially during the treatment period of up to 65 weeks (Table 4).”
Quote in the paperSubstantial claim - Findingown data
The mean number of spotting-only days and episodes and the duration of spotting-only episodes similarly showed progressive decreases with continued dienogest 2 mg treatment.
“The mean number of spotting-only days and episodes and the duration of spotting-only episodes similarly showed progressive decreases with continued dienogest 2 mg treatment.”
Quote in the paperSubstantial claim - Findingown data
The bleeding patterns of women in the dienogest 2 mg group more closely resembled placebo-treated than LA-treated women during WHO reference period 1 (months 1-3).
“The bleeding patterns of women in the dienogest 2 mg group more closely resembled placebo-treated than LA-treated women during World Health Organization reference period 1 (months 1–3) (Table 5).”
Quote in the paperNot a substantial claim - Findingown data
In total, 18 AEs in 15 (4.5%) women led to study discontinuation.
“In total, 18 AEs in 15 (4.5%) women led to study discontinuation (Table 2).”
Quote in the paperSubstantial claim - Findingown data
Body weight increased slightly over time in all treatment groups (including placebo) during treatment for up to 24 weeks.
“Body weight increased slightly over time in all treatment groups (including the placebo group) during treatment for up to 24 weeks.”
Quote in the paperNot a substantial claim - Findingcitation
Headache was reported in 21.1% of LA-treated women in the active comparator study.
“By contrast, headache was reported in 21.1% of LA-treated women in the active comparator study, while “hypoestrogenic” ADRs were also common in the LA group, including vulvovaginal dryness (7.0%), loss of libido (6.3%), and hot flushes (6.3%).12”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- Findingown data
In total, 12 SAEs were reported in 11 women in the pooled dienogest 2 mg group.
“In total, 12 SAEs were reported in 11 women in the pooled dienogest 2 mg group.”
Quote in the paperNot a substantial claim - Findingcitation
The adverse events associated with dienogest 2 mg decreased in both incidence and intensity over time.
“In addition, the AEs associated with dienogest 2 mg decreased in both incidence and intensity over time.10–12”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- Findingown data
Hematology, blood chemistry, and liver enzyme parameters remained generally stable in the pooled dienogest 2 mg group, as well as the comparator groups.
“Hematology, blood chemistry, and liver enzyme parameters remained generally stable in the pooled dienogest 2 mg group, as well as the comparator groups.”
Quote in the paperSubstantial claim - Findingown data
This analysis of pooled data from the dienogest clinical program in Europe confirms and further characterizes the favorable safety and tolerability profile of dienogest 2 mg for short- and long-term use.
“This analysis of pooled data from the dienogest clinical program in Europe confirms and further characterizes the favorable safety and tolerability profile of dienogest 2 mg for short- and long-term use that was demonstrated in the individual trials.”
Quote in the paperSubstantial claim- Rests on an assumption: The four trials together included women who are representative of the wider population of endometriosis patients.
- Study design and conductnone given
The four trials used similar methodologies for data collection and analysis.
“These well-designed studies used similar methodologies for data collection and analysis, and together included large numbers of women who are representative of the wider population of endometriosis patients.”
Quote in the paperSubstantial claim - Premisecitation
Pain intensity decreased progressively from baseline and continued to decrease during long-term dienogest therapy over more than 1 year.
“Pain intensity, measured on a visual analog scale, decreased progressively from baseline and continued to decrease during long-term therapy over more than 1 year.”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
- Premisecitation
Surgery for endometriosis has high recurrence rates: approximately 40%-50% after 5 years.
“Surgery is a common treatment choice, but recurrence rates are high: approximately 40%–50% after 5 years.2,3”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [2] Guo SW Recurrence of endometriosis and its control Hum Reprod Update 2009 15 4 441 461 19279046
Not checked in the free run.
- cites [3] Vercellini P Crosignani PG Abbiati A Somigliana E Vigano P Fedele L The effect of surgery for symptomatic endometriosis: the other side of the story Hum Reprod Update 2009 15 2 177 188 19136455
Not checked in the free run.
- Premisecitation
Dienogest 2 mg once daily was reported in the four key European trials to be generally safe and well tolerated for the treatment of endometriosis.
“Dienogest 2 mg once daily was reported in these trials to be generally safe and well tolerated for the treatment of endometriosis.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
- Premisecitation
Approved medical treatments for endometriosis, GnRH analogs and danazol, are associated with suboptimal safety and tolerability that limit their long-term use.
“Approved medical treatments for relief of the symptoms of endometriosis include gonadotropin-releasing hormone (GnRH) analogs and the androgen, danazol. Both these classes of treatment, however, are associated with suboptimal safety and tolerability that limit their long-term use.4,5”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [4] Mounsey AL Wilgus A Slawson DC Diagnosis and management of endometriosis Am Fam Physician 2006 74 4 594 600 16939179
Not checked in the free run.
- cites [5] Luciano AA Danazol treatment of endometriosis-associated pain J Minim Invasive Gynecol 2006 13 6 523 524 17097573
Not checked in the free run.
- Study design and conductnone given
The participants were generally similar with regard to demographics and history across the four trials.
“The participants were generally similar with regard to demographics and history across the four trials.”
Quote in the paperNot a substantial claim - Interpretationown data
The bleeding pattern associated with dienogest 2 mg was well tolerated.
“The bleeding pattern associated with dienogest 2 mg was generally well tolerated, and only two women (0.6%) reported bleeding events as the primary reason for premature discontinuation (diary data on bleeding patterns are described).”
Quote in the paperSubstantial claim - Premisecitation
In comparison to progestins with androgenic activity such as medroxyprogesterone acetate and norethindrone acetate, dienogest has a more favorable profile with low incidences of androgenic effects.
“In comparison to progestins with androgenic activity such as medroxyprogesterone acetate and norethindrone acetate,18–20 dienogest has a more favorable profile with low incidences of androgenic effects.10–13,21–23”
Quote in the paperSubstantial claim0 of 10 sources checked- cites [18] Ghatge RP Jacobsen BM Schittone SA Horwitz KB The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells Breast Cancer Res 2005 7 6 R1036 R1050 16457685 PMC1410743
Not checked in the free run.
- cites [19] Soares SR Martinez-Varea A Hidalgo-Mora JJ Pellicer A Pharmacologic therapies in endometriosis: a systematic review Fertil Steril 2012 98 3 529 555 22938768
Not checked in the free run.
- cites [20] Vercellini P Pietropaolo G De GO Pasin R Chiodini A Crosignani PG Treatment of symptomatic rectovaginal endometriosis with an estrogen-progestogen combination versus low-dose norethindrone acetate Fertil Steril 2005 84 5 1375 1387 16275232
Not checked in the free run.
- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
- cites [21] Cosson M Querleu D Donnez J Dienogest is as effective as triptorelin in the treatment of endometriosis after laparoscopic surgery: results of a prospective, multicenter, randomized study Fertil Steril 2002 77 4 684 692 11937116
Not checked in the free run.
- cites [22] McCormack PL Dienogest: a review of its use in the treatment of endometriosis Drugs 2010 70 16 2073 2088 20964453
Not checked in the free run.
- cites [23] Mueck AO Dienogest: an oral progestogen for the treatment of endometriosis Expert Rev Obstet Gynecol 2011 6 1 5 15
Not checked in the free run.
- Interpretationcitation
The safety profile of dienogest in endometriosis demonstrated in these pooled analyses is supported by other published studies.
“The safety profile of dienogest in endometriosis that is demonstrated in these pooled analyses is supported by other published studies.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [28] Schindler AE Henkel A Moore C Oettel M Effect and safety of high-dose dienogest (20 mg/day) in the treatment of women with endometriosis Arch Gynecol Obstet 2010 282 5 507 514 20012981
Not checked in the free run.
- cites [29] Momoeda M Taketani Y Randomized double-blind, multicentre, parallel-group dose-response study of dienogest in patients with endometriosis Jpn Pharmacol Ther 2007 35 7 769 783
Not checked in the free run.
- cites [30] Harada T Momoeda M Taketani Y Dienogest is as effective as intranasal buserelin acetate for the relief of pain symptoms associated with endometriosis – a randomized, double-blind, multicenter, controlled trial Fertil Steril 2009 91 3 675 681 18653184
Not checked in the free run.
- Premisecitation
Even at a high dose of 20 mg/day for 24 weeks, dienogest had no clinically relevant impact on laboratory measures including glucose and lipid metabolism, liver function, electrolyte balance, and hematology.
“Even at a high dose of 20 mg/day for 24 weeks, dienogest had no clinically relevant impact on laboratory measures including glucose and lipid metabolism, liver function, electrolyte balance, and hematology.28”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Schindler AE Henkel A Moore C Oettel M Effect and safety of high-dose dienogest (20 mg/day) in the treatment of women with endometriosis Arch Gynecol Obstet 2010 282 5 507 514 20012981
Not checked in the free run.
- Interpretationreasoning
The pharmacological properties of dienogest contribute to the absence of clinically relevant androgenic effects.
“The pharmacological properties of dienogest, which have been described in detail elsewhere, contribute to the absence of clinically relevant androgenic effects.”
Quote in the paperSubstantial claim
- May combine two claims. 21
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 5
May combine two claims.
Findingown dataEach of the most common adverse drug reactions occurred in <10% of women, with headache being the most common at 9.0%.
“Each ADR was reported in <10% of women, with headache being the most common (9.0%).”
Quote in the paperSubstantial claimThe quote only partly states this claim.
Findingown dataLaboratory and vital sign assessments indicated no safety concerns for dienogest 2 mg.
“Laboratory and vital sign assessments indicated no safety concerns for dienogest.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIncidences of hypoestrogenic ADRs in the pooled dienogest 2 mg population were vulvovaginal dryness (0.6%), loss of libido (1.5%), and hot flushes (2.7%).
“Incidences of “hypoestrogenic” ADRs in the pooled population treated with dienogest 2 mg were: vulvovaginal dryness (0.6%), loss of libido (1.5%), and hot flushes (2.7%).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe mean number of bleeding/spotting days, number of bleeding/spotting episodes, and duration of bleeding/spotting episodes all decreased progressively during continued dienogest 2 mg treatment through WHO 90-day reference periods 1-5 (up to 15 months).
“The mean (and median) number of bleeding/spotting days, number of bleeding/spotting episodes, and duration of bleeding/spotting episodes all decreased progressively during continued dienogest 2 mg treatment, ie, through World Health Organization 90-day reference periods 1–5 (up to 15 months).”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationStudy discontinuation rates associated with dienogest 2 mg were broadly consistent across studies, including the long-term extension study, and were similar to those reported for LA in the 24-week active comparator-controlled study (12 events in 5 [3.9%] women).
“The study discontinuation rates associated with dienogest 2 mg were broadly consistent across studies, including the long-term extension study and were similar to those reported for LA in the 24-week active comparator-controlled study (ie, 12 events in 5 [3.9%] women).11,12”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
May combine two claims.
FindingcitationMean blood lipid concentrations in the pooled dienogest 2 mg group were similar to placebo-treated women and remained stable over up to 65 weeks.
“Mean concentrations of blood lipids (ie, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol) in the pooled dienogest 2 mg group were similar to lipid concentrations in placebo-treated women,11 and they remained stable over a treatment period of up to 65 weeks13 (Table 4).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
May combine two claims.
FindingcitationMean glycated hemoglobin levels were stable over time in the pooled dienogest 2 mg group and similar to normal-range levels reported for LA and placebo.
“Mean glycated hemoglobin levels were stable over time in the pooled dienogest 2 mg group (Table 4) and were similar to the normal-range glycated hemoglobin levels reported for LA and placebo in the individual studies.11,12”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
May combine two claims.
FindingcitationWomen treated with dienogest 2 mg showed similar mean estradiol levels at 12 weeks compared to placebo, whereas LA-treated women showed a marked decrease in mean estradiol concentrations from 299.0 pmol/L at baseline to 68.5 pmol/L after 24 weeks.
“Women treated with dienogest 2 mg showed similar mean estradiol levels at 12 weeks compared to women treated with placebo, whereas LA-treated women showed a marked decrease in mean estradiol concentrations from 299.0 pmol/L (81.5 pg/mL) at baseline to 68.5 pmol/L (18.7 pg/mL) after 24 weeks.11,12”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
May combine two claims.
Findingown dataThe current pooled analysis shows that an initial increase in the number of bleeding/spotting days and a desynchronized bleeding pattern with dienogest treatment is followed by a progressive reduction in bleeding days during continued treatment, accompanied by increases in amenorrhea rates.
“The current pooled analysis shows that an initial increase in the number of bleeding/spotting days and a desynchronized bleeding pattern with dienogest treatment is followed by a progressive reduction in bleeding days during continued treatment, accompanied by increases in amenorrhea rates.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationHypoestrogenic ADRs in the LA group included vulvovaginal dryness (7.0%), loss of libido (6.3%), and hot flushes (6.3%).
“By contrast, headache was reported in 21.1% of LA-treated women in the active comparator study, while “hypoestrogenic” ADRs were also common in the LA group, including vulvovaginal dryness (7.0%), loss of libido (6.3%), and hot flushes (6.3%).12”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
May combine two claims.
Findingown dataMean heart rate and blood pressure were relatively stable over time in the pooled dienogest 2 mg group, as they were in the comparator groups.
“Mean heart rate and blood pressure were relatively stable over time in the pooled dienogest 2 mg group (Table 4), as they were in the comparator groups.”
Quote in the paperSubstantial claimMay combine two claims.
FindingcitationLA-treated women showed increases in bone turnover markers and a clinically relevant reduction in lumbar spine BMD (−4.04% for LA versus +0.25% for dienogest 2 mg at 24 weeks).
“LA-treated women showed increases in bone turnover markers and a clinically relevant reduction in lumbar spine BMD (ie, −4.04% for LA, versus +0.25% for dienogest 2 mg at 24 weeks).12”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
May combine two claims.
Findingown dataThe current pooled analysis demonstrates that mean weight change during continued dienogest 2 mg treatment is small and is not substantially different from that observed during placebo treatment.
“The current pooled analysis demonstrates that mean weight change during continued dienogest 2 mg treatment is small and is not substantially different from that observed during placebo treatment.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
Study design and conductnone givenSafety analyses included women who took study medication at least once and for whom at least one post-baseline observation was available (full analysis set).
“In all four studies, the safety analyses included women who took study medication at least once and for whom at least one post-baseline observation was available (ie, the “full analysis set”).”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationDienogest offers unique pharmacologic benefits relevant to endometriosis, including potent progestogenic effects leading to effective endometrial lesion reduction, moderate suppression of estrogen levels, and no significant androgenic, mineralocorticoid, or glucocorticoid activity.
“Dienogest offers unique pharmacologic benefits relevant to the treatment of endometriosis, including potent progestogenic effects that lead to effective endometrial lesion reduction, combined with only moderate suppression of estrogen levels and no significant androgenic, mineralocorticoid, or glucocorticoid activity.7–9”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [7] Oettel M Breitbarth H Elger W The pharmacological profile of dienogest Eur J Contracept Reprod Health Care 1999 4 1 suppl 1 2 13 1362 5187
Not checked in the free run.
- cites [8] Sasagawa S Shimizu Y Kami H Dienogest is a selective progesterone receptor agonist in transactivation analysis with potent oral endometrial activity due to its efficient pharmacokinetic profile Steroids 2008 73 2 222 231 18061638
Not checked in the free run.
- cites [9] Harada T Taniguchi F Dienogest: a new therapeutic agent for the treatment of endometriosis Womens Health (Lond Engl) 2010 6 1 27 35 20001868
Not checked in the free run.
May combine two claims.
PremisecitationProgestins offer long-term efficacy but can cause weight gain or androgenic effects at the high doses required for efficacy.
“A number of progestins offer long-term efficacy but, depending on their pharmacologic profile, can cause weight gain or androgenic effects at the high doses required for efficacy.6”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [6] Vercellini P Fedele L Pietropaolo G Frontino G Somigliana E Crosignani PG Progestogens for endometriosis: forward to the past Hum Reprod Update 2003 9 4 387 396 12926531
Not checked in the free run.
May combine two claims.
Interpretationown dataDienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency.
“Estradiol levels were maintained within the low-physiological range, in support of previous evidence indicating that dienogest 2 mg demonstrates therapeutic efficacy without inducing estradiol deficiency.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationIn four key European trials, dienogest 2 mg once daily demonstrated significant efficacy for lesion reduction and reduction in pain intensity superior to placebo and equivalent to a GnRH analog.
“In the four key European trials, dienogest at a dose of 2 mg once daily demonstrated significant efficacy for lesion reduction assessed at laparoscopy and a reduction in pain intensity that was significantly superior to placebo and equivalent to a GnRH analog.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll trials had full approval from ethics committees according to the German Medicines Act (AMG).
“All trials had full approval from ethics committees according to the German Medicines Act (AMG).”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductreasoningAll women who took study medication at least once were included in the current pooled analyses (full analysis set).
“Following the intent-to-treat principle, all women who took study medication at least once were included in the current pooled analyses (full analysis set).”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThese analyses show that dienogest 2 mg is a well-tolerated therapy with a favorable safety profile that is suitable for long-term use.
“These analyses show that dienogest 2 mg is a well-tolerated therapy with a favorable safety profile that is suitable for long-term use.”
Quote in the paperSubstantial claim- Rests on an assumption: The four trials together included women who are representative of the wider population of endometriosis patients.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDienogest demonstrates a well-characterized, favorable safety and tolerability profile in combination with estradiol for indications including contraception and hormone replacement therapy for menopausal symptoms.
“Dienogest also demonstrates a well-characterized, favorable safety and tolerability profile in combination with estradiol for indications including contraception and hormone replacement therapy for menopausal symptoms.32–37”
Quote in the paperNot a substantial claim0 of 6 sources checked- cites [32] Palacios S Wildt L Parke S Machlitt A Romer T Bitzer J Efficacy and safety of a novel oral contraceptive based on oestradiol (oestradiol valerate/dienogest): a phase III trial Eur J Obstet Gynecol Reprod Biol 2010 149 1 57 62 19969409
Not checked in the free run.
- cites [33] Perez-Campos EF Ethinylestradiol/dienogest in oral contraception Drugs 2010 70 6 681 689 20394455
Not checked in the free run.
- cites [34] von Schoultz B Clinical efficacy and safety of combined estradiol valerate and dienogest: a new no-bleed treatment Climacteric 2003 6 suppl 2 24 32 14669841
Not checked in the free run.
- cites [35] Wellington K Perry CM Estradiol valerate/dienogest Drugs 2002 62 3 491 504 11827562
Not checked in the free run.
- cites [36] Wiegratz I Stahlberg S Manthey T Effects of combined oral contraceptive ethinyl estradiol (30 microg) and dienogest (2 mg) on carbohydrate metabolism during 1 year of conventional or extended-cycle use Horm Metab Res 2010 42 5 358 363 20213585
Not checked in the free run.
- cites [37] Wiegratz I Stahlberg S Manthey T Effects of an oral contraceptive containing 30 mcg ethinyl estradiol and 2 mg dienogest on lipid metabolism during 1 year of conventional or extended-cycle use Contraception 2010 81 1 57 61 20004274
Not checked in the free run.
May combine two claims.
Premiseown dataThe favorable profile of dienogest 2 mg is combined with an efficacy equivalent to the highest current treatment standards and offers a progressive improvement in pain during continued use.
“This favorable profile of dienogest 2 mg is combined with an efficacy equivalent to the highest current treatment standards and offers a progressive improvement in pain during continued use.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [10] Kohler G Faustmann TA Gerlinger C Seitz C Mueck AO A dose-ranging study to determine the efficacy and safety of 1, 2, and 4 mg of dienogest daily for endometriosis Int J Gynaecol Obstet 2010 108 1 21 25 19819448
Not checked in the free run.
- cites [11] Strowitzki T Faustmann T Gerlinger C Seitz C Dienogest in the treatment of endometriosis-associated pelvic pain: a 12-week, randomized, double-blind, placebo-controlled study Eur J Obstet Gynecol Reprod Biol 2010 151 2 193 198 20444534
Not checked in the free run.
- cites [12] Strowitzki T Marr J Gerlinger C Faustmann T Seitz C Dienogest is as effective as leuprolide acetate in treating the painful symptoms of endometriosis: a 24-week, randomized, multicentre, open-label trial Hum Reprod 2010 25 3 633 641 20089522
Not checked in the free run.
- cites [13] Petraglia F Hornung D Seitz C Reduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment Arch Gynecol Obstet 2012 285 1 167 173 21681516 PMC3249203
Not checked in the free run.
May combine two claims.
Study design and conductown dataOverall, 89.2% of women treated with dienogest 2 mg completed the planned study durations, including 90.5% who completed the long-term extension study.
“Overall, 89.2% of women treated with dienogest 2 mg completed the planned study durations, including 90.5% who completed the long-term extension study.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataDienogest 2 mg is well tolerated by women in light of its efficacy for pain relief.
“Notably, the number of discontinuations due to heavy or irregular bleeding was low (ie, 2 of 332 women), indicating that dienogest 2 mg is well tolerated by women in light of its efficacy for pain relief.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationGuidelines from the World Endometriosis Society have recommended dienogest as an empirical treatment option for women without laparoscopic confirmation and as a suitable adjuvant therapy following endometriosis surgery.
“Reflecting these observations, the guidelines from the World Endometriosis Society have recommended dienogest as an empirical treatment option for women without laparoscopic confirmation and as a suitable adjuvant therapy following endometriosis surgery.38”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [38] Johnson NP Hummelshoj L Consensus on current management of endometriosis Hum Reprod 2013 28 6 1552 1568 23528916
Not checked in the free run.
The paper relies on this without support.
There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis.
“There is a paucity of randomized trial evidence to support the use of many treatments in endometriosis.”
“For many of the medical treatments that are available, there is a paucity of randomized clinical trial evidence on which to base guideline recommendations.”
The paper relies on this without support.
The four trials together included women who are representative of the wider population of endometriosis patients.
“These well-designed studies used similar methodologies for data collection and analysis, and together included large numbers of women who are representative of the wider population of endometriosis patients.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In a pooled analysis of four randomized controlled European trials, DNG's most common adverse reactions were headache (9%), breast discomfort (5.4%), depressed mood (5.1%), and acne (5.1%); bleeding pattern was well-tolerated and only 0.6% reported bleeding events as main cause for premature discontinuation.
“In a pooled analysis of four randomized, controlled, European trials [38] the most common adverse reactions were headache (9%), breast discomfort (5.4%) depressed mood (5.1%), and acne (5.1%).”
From Oral and depot progestin therapy for endometriosis: towards a personalized medicine (2017) · cites this paper as [38]
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“Surgery is a common treatment choice, but recurrence rates are high: approximately 40%–50% after 5 years.(2,3) correspondence: Thomas strowitzki Department of gynecological endocrinology and reproductive Medicine, University of Heidelberg, Voßstraße 9, 69115 Heidelberg, germany Tel +49 62 2156 7910 Fax +49 62 2156 409…”
Consensus on current management of endometriosis
Johnson, N. P., Hummelshoj, L., for the World Endometriosis Society Montpellier Consortium, Abrao, M. S., Adamson, G. D., Allaire, C., Amelung, V., Andersson, E., Becker, C., Birna Árdal, K. B., et al. (2013) · Human Reproduction · doi:10.1093/humrep/det050 · Cited by 558 · cited 1× · see citing works
“Reflecting these observations, the guidelines from the World Endometriosis Society have recommended dienogest as an empirical treatment option for women without laparoscopic confirmation and as a suitable adjuvant therapy following endometriosis surgery.(38)”
Self-citationStrowitzki, T., Marr, J., Gerlinger, C., Faustmann, T., & Seitz, C. (2010) · Human Reproduction · doi:10.1093/humrep/dep469 · Cited by 381 · cited 6× · see citing works
“Bone metabolism and BMD As previously reported, dienogest 2 mg was associated with minimal changes in bone turnover markers (bone alkaline phosphatase, osteocalcin, and urinary CrossLaps) and in lumbar spine BMD at 24 weeks.(12) LA-treated women showed increases in bone turnover markers and a clinically relevant reduc…”
InfluentialSelf-citationThe effect of surgery for symptomatic endometriosis: the other side of the story
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“Surgery is a common treatment choice, but recurrence rates are high: approximately 40%–50% after 5 years.(2,3) correspondence: Thomas strowitzki Department of gynecological endocrinology and reproductive Medicine, University of Heidelberg, Voßstraße 9, 69115 Heidelberg, germany Tel +49 62 2156 7910 Fax +49 62 2156 409…”
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“These include a pilot study of high-dose dienogest (20 mg/day) in Europe 28 and a Phase II dose-ranging study, 29 a Phase III comparator-controlled trial using the GnRH analog, buserelin acetate, 30 and two long-term studies 16,31 in Japan.”
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“Mean glycated hemoglobin levels were stable over time in the pooled dienogest 2 mg group (Table 4) and were similar to the normal-range glycated hemoglobin levels reported for LA and placebo in the individual studies.(11,12) Mean estradiol levels in the pooled dienogest 2 mg group did not change substantially during t…”
Self-citationReduced pelvic pain in women with endometriosis: efficacy of long-term dienogest treatment
Petraglia, F., Hornung, D., Seitz, C., Faustmann, T., Gerlinger, C., Luisi, S., Lazzeri, L., & Strowitzki, T. (2012) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-011-1941-7 · Cited by 200 · cited 1× · see citing works
“In 10–13,21– Laboratory and vital sign assessments in the pooled safety population indicated no safety concerns for dienogest 2 mg.”
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“6,16,24 Weight gain is a common adverse effect of progestins including medroxyprogesterone acetate and norethindrone acetate 6,20,26,27 and is often perceived adversely by patients.”
Long‐term use of dienogest for the treatment of endometriosis
Momoeda, M., Harada, T., Terakawa, N., Aso, T., Fukunaga, M., Hagino, H., & Taketani, Y. (2009) · Journal of Obstetrics and Gynaecology Research · doi:10.1111/j.1447-0756.2009.01076.x · Cited by 192 · cited 1× · see citing works
“The pharmacodynamic study also reported, alongside other studies, that normal ovarian function returns promptly following the cessation of dienogest treatment.(6,16,24) Weight gain is a common adverse effect of progestins including medroxyprogesterone acetate and norethindrone acetate(6,20,26,27) and is often perceive…”
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Progestogens for endometriosis: forward to the past
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“Changes in bleeding pattern are another well-recognized characteristic of many progestins.(6) The current pooled analysis shows that an initial increase in the number of bleeding/ spotting days and a desynchronized bleeding pattern with dienogest treatment is followed by a progressive reduction in bleeding days during…”
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Dienogest: A New Therapeutic Agent for the Treatment of Endometriosis
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“However, the pharmacodynamic trial in healthy women, which measured serum estradiol levels every third day, may provide a more accurate representation of the effects of dienogest 2 mg when compared with the sporadic assessments of serum estradiol levels performed in the patient trials, and readers are, therefore, refe…”
Self-citationMedical management of endometriosis-associated pain
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Lipid Metabolism During Treatment of Endometriosis with the Progestin Dienogest
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Clinical efficacy and safety of combined estradiol valerate and dienogest: a new no-bleed treatment.
von Schoultz, B. (2003) · PubMed · Cited by 12 · see citing works
Danazol treatment of endometriosis-associated pain
Luciano, A. A. (2006) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2006.06.026 · Cited by 12 · cited 1× · see citing works
“Both these classes of treatment, however, are associated with suboptimal safety and tolerability that limit their long-term use.(4,5) A number of progestins offer long-term efficacy but, depending on their pharmacologic profile, can cause weight gain or androgenic effects at the high doses required for efficacy.”
REES, M. C. P. (2002) · Drugs · doi:10.2165/00003495-200262030-00008 · Cited by 3 · see citing works
Flagged first, then by citations
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Endometriosis: where are we and where are we going?
Greene, A. D., Lang, S. A., Kendziorski, J. A., Sroga-Rios, J. M., Herzog, T. J., & Burns, K. A. (2016) · Reproduction · doi:10.1530/rep-16-0052 · Cited by 187 · see citing works
Current and emerging treatment options for endometriosis
Ferrero, S., Evangelisti, G., & Barra, F. (2018) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2018.1494154 · Cited by 152 · see citing works
Bedaiwy, M. A., Allaire, C., & Alfaraj, S. (2017) · Fertility and Sterility · doi:10.1016/j.fertnstert.2016.12.024 · Cited by 126 · see citing works
Vercellini, P., Bracco, B., Mosconi, P., Roberto, A., Alberico, D., Dhouha, D., & Somigliana, E. (2016) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.11.016 · Cited by 127 · see citing works
Use of dienogest in endometriosis: a narrative literature review and expert commentary
Murji, A., Biberoglu, K. O., Leng, J., Mueller, M. D., Römer, T., Vignali, M., & Yarmolinskaya, M. I. (2020) · Current Medical Research and Opinion · doi:10.1080/03007995.2020.1744120 · Cited by 123 · see citing works
Barra, F., Scala, C., & Ferrero, S. (2018) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2018.1461840 · Cited by 100 · see citing works
Römer, T. (2018) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-018-4864-8 · Cited by 82 · see citing works
Safety of medical treatments for endometriosis
Berlanda, N., Somigliana, E., Viganò, P., & Vercellini, P. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1121991 · Cited by 78 · see citing works
Endometrial preparation with Dienogest before hysteroscopic surgery: a systematic review
Laganà, A. S., Vitale, S. G., Muscia, V., et al. (2016) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-016-4244-1 · Cited by 76 · see citing works
“Several clinical studies show that this novel synthetic progestin has a favorable safety profile [20], exerts comprehensive inhibition of extra-ovarian and peripheral estrogen production through inhibition of aromatase and 17b-hydroxysteroid dehydrogenase 1 (HSD17B1) [21, 22], increases apoptosis of endometriotic cell…”
BackgroundClinical dynamics of Dienogest for the treatment of endometriosis: from bench to bedside
Laganà, A. S., Vitale, S. G., Granese, R., Palmara, V. I., Frangež, H. B., Bokal, E. V., Chiofalo, B., & Triolo, O. (2017) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2017.1297421 · Cited by 70 · see citing works
Lang, J., Yu, Q., Zhang, S., Li, H., Gude, K., Ludwig, C., Ren, X., & Dong, L. (2017) · Journal of Women s Health · doi:10.1089/jwh.2017.6399 · Cited by 64 · see citing works
“26 A limitation of the double-blind phase of this study is the relatively short (24-week) treatment duration, as prolonged placebo treatment would be difficult to justify in women experiencing chronic pain.”
InfluentialLong‐term dienogest administration in patients with symptomatic adenomyosis
Neriishi, K., Hirata, T., Fukuda, S., Izumi, G., Nakazawa, A., Yamamoto, N., Harada, M., Hirota, Y., Koga, K., Wada‐Hiraike, O., et al. (2018) · Journal of obstetrics and gynaecology research · doi:10.1111/jog.13674 · Cited by 62 · see citing works
“effect of dienogest after 52 or 65 weeks of treatment.(10,12,15) Our result was consistent with that of the previous reports, and we showed that dienogest is”
ResultOral and depot progestin therapy for endometriosis: towards a personalized medicine
Buggio, L., Somigliana, E., Barbara, G., Frattaruolo, M. P., & Vercellini, P. (2017) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2017.1381086 · Cited by 58 · see citing works
“In a pooled analysis of four randomized, controlled, European trials [38], the most common adverse reactions were headache (9%), breast discomfort (5.”
BackgroundReal world data on symptomology and diagnostic approaches of 27,840 women living with endometriosis
Becker, K., Heinemann, K., Imthurn, B., Marions, L., Moehner, S., Gerlinger, C., Serrani, M., & Faustmann, T. A. (2021) · Scientific Reports · doi:10.1038/s41598-021-99681-3 · Cited by 56 · see citing works
Self-citationAdachi, K., Takahashi, K., Nakamura, K., Otake, A., Sasamoto, N., Miyoshi, Y., Shioji, M., Yamamoto, Y., Fujitani, M., Wakimoto, A., et al. (2016) · Gynecological Endocrinology · doi:10.3109/09513590.2016.1147547 · Cited by 53 · see citing works
“In one randomized controlled trial, dienogest was well tolerated and had a favorable safety profile465 weeks in patients with endometriosis [14].”
BackgroundCeccaroni, M., Clarizia, R., Liverani, S., Donati, A., Ceccarello, M., Manzone, M., Roviglione, G., & Ferrero, S. (2021) · Gynecological Endocrinology · doi:10.1080/09513590.2021.1929151 · Cited by 56 · see citing works
“In four RCT, Dienogest was well tolerated with a good safety profile [17,18].”
BackgroundEffect of Dienogest therapy on the size of the endometrioma
Vignali, M., Belloni, G. M., Pietropaolo, G., Barbasetti Di Prun, A., Barbera, V., Angioni, S., & Pino, I. (2020) · Gynecological Endocrinology · doi:10.1080/09513590.2020.1725965 · Cited by 50 · see citing works
Dienogest reduces endometrioma volume and endometriosis-related pain symptoms
Uludağ, S. Z., Demirtaş, E., Şahin, Y., & Aygen, E. (2021) · Journal of Obstetrics and Gynaecology · doi:10.1080/01443615.2020.1867962 · Cited by 49 · see citing works
“Similar to our work, Strowitzki et al. (2015) reported that mean oestradiol level in the pooled dienogest 2mg group did not change substantially during the treatment period of up to 65weeks.”
ResultEffectiveness of Dienogest for Treatment of Recurrent Endometriosis: Multicenter Data
Lee, J. H., Song, J. Y., Yi, K. W., Lee, S. R., Lee, D.-Y., Shin, J.-H., Cho, S., Seo, S. K., & Kim, S. H. (2018) · Reproductive Sciences · doi:10.1177/1933719118779733 · Cited by 44 · see citing works
“4%).(10) In contrast, in the present study, only 2 (1.”
ResultCho, B., Roh, J.-W., Park, J., Jeong, K., Kim, T.-H., Kim, Y. S., Kwon, Y.-S., Cho, C.-H., Park, S. H., & Kim, S. H. (2020) · Reproductive Sciences · doi:10.1007/s43032-019-00094-5 · Cited by 44 · see citing works
Yamanaka, A., Hada, T., Matsumoto, T., Kanno, K., Shirane, A., Yanai, S., Nakajima, S., Ebisawa, K., Ota, Y., & Andou, M. (2017) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2017.07.014 · Cited by 43 · see citing works
Tolerability considerations for gonadotropin-releasing hormone analogues for endometriosis
Corte, L. D., Barra, F., Mercorio, A., Evangelisti, G., Rapisarda, A. M. C., Ferrero, S., Bifulco, G., & Giampaolino, P. (2020) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1080/17425255.2020.1789591 · Cited by 44 · see citing works
Clinical experience of long-term use of dienogest after surgery for ovarian endometrioma
Chandra, A., Rho, A. M., Jeong, K., Yu, T., Jeon, J. H., Park, S. Y., Lee, S. R., Moon, H. S., & Chung, H. W. (2018) · Obstetrics & Gynecology Science · doi:10.5468/ogs.2018.61.1.111 · Cited by 41 · see citing works
“[19] showed the results that dienogest can be safely used over a period extending up to 65 weeks.”
ResultLaganà, A. S., Giacobbe, V., Triolo, O., Granese, R., Frangež, H. B., Bokal, E. V., Ietto, C., & Palmara, V. I. (2016) · Gynecological Endocrinology · doi:10.3109/09513590.2015.1128409 · Cited by 38 · see citing works
“medical treatment of endometriosis: several studies already showed that this novel synthetic progestin has a favorable safety profile [13], exerts comprehensive inhibition of abnormal estrogen production through inhibition of aromatase and 17b-hydroxysteroid dehydrogenase 1 (HSD17b1) [14], increases apoptosis of endom…”
BackgroundTechatraisak, K., Hestiantoro, A., Ruey, S., Banal-Silao, M. J., Kim, M.-R., Seong, S. J., Thaufik, S., Ahlers, C., Shin, S. Y., & Lee, B. S. (2019) · BMC Women's Health · doi:10.1186/s12905-019-0758-6 · Cited by 36 · see citing works
Self-citationFlavonoids Quercetin and Kaempferol Are NR4A1 Antagonists and Suppress Endometriosis in Female Mice
Zhang, L. J., Mohankumar, K., Martin, G., Mariyam, F., Park, Y., Han, S. J., & Safe, S. H. (2023) · Endocrinology · doi:10.1210/endocr/bqad133 · Cited by 36 · see citing works
Lee, D.-Y., Lee, J.-Y., Seo, J.-W., Yoon, B.-K., & Choi, D. (2016) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-016-4184-9 · Cited by 36 · see citing works
“Moreover, the high standard deviation of estradiol levels in studies indicates that there is a substantial degree of variability between individuals [22].”
BackgroundHormonal Treatment of Endometriosis: A Narrative Review
Piriyev, E., Schiermeier, S., & Römer, T. (2025) · Pharmaceuticals · doi:10.3390/ph18040588 · Cited by 34 · see citing works
“Dienogest is a progestin available as a monotherapy for the treatment of endometriosis, which has also shown good efficacy in studies with regard to pain symptoms and has been found to be equally effective as GnRH analogues over a period of 6 months [34,35].”
Techatraisak, K., Hestiantoro, A., Soon, R., Banal-Silao, M. J., Kim, M.-R., Seong, S. J., Hidayat, S. T., Cai, L., Shin, S., & Lee, B. S. (2022) · Reproductive Sciences · doi:10.1007/s43032-021-00787-w · Cited by 31 · see citing works
“Overall, the share of patients with normal bleeding profile decreased while proportion of patients with amenorrhea increased during the study which is in line with current evidence on dienogest profile [7, 15, 17, 18, 42, 48].”
ResultIwami, N., Kawamata, M., Ozawa, N., Yamamoto, T., Watanabe, E., Mizuuchi, M., Moriwaka, O., & Kamiya, H. (2020) · Reproductive Biology · doi:10.1016/j.repbio.2020.100470 · Cited by 30 · see citing works
Nirgianakis, K., Vaineau, C., Agliati, L., McKinnon, B. D., Gasparri, M. L., & Mueller, M. D. (2020) · Acta Obstetricia Et Gynecologica Scandinavica · doi:10.1111/aogs.13969 · Cited by 29 · see citing works
Coincidence of uterine malformations and endometriosis: a clinically relevant problem?
Piriyev, E., & Römer, T. (2020) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-020-05750-9 · Cited by 28 · see citing works
Prieto, D. M. M., Herrmann, J., Osterwald, H., Kochhar, P. S., Schleußner, E., Markert, U. R., & Oettel, M. (2018) · Reproductive Biology · doi:10.1016/j.repbio.2018.07.002 · Cited by 26 · see citing works
Song, S. Y., Park, M., Lee, G. W., Lee, K. H., Chang, H. K., Kwak, S. M., & Yoo, H. J. (2018) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2018.10.014 · Cited by 24 · see citing works
Leonardo-Pinto, J. P., Benetti‐Pinto, C. L., & Yela, D. A. (2018) · Journal of Sex & Marital Therapy · doi:10.1080/0092623x.2018.1474411 · Cited by 23 · see citing works
“The sample size calculation was based on prior studies with DNG as treatment for endometriosis (Harada & Taniguchi, 2010; Momoeda et al., 2009; Strowitzki et al., 2015).”
MethodDienogest in endometriosis treatment: A narrative literature review
Lee, J., Park, H. J., & Yi, K. W. (2023) · Daehan saengsik uihak hoeji/Clinical and experimental reproductive medicine · doi:10.5653/cerm.2023.06128 · Cited by 24 · see citing works
“Changes in bleeding patterns associated with DNG are generally well tolerated and are unlikely to be the primary reason for DNG discontinuation [14,37].”
BackgroundMethodManagement of women with endometriosis in the 21st century
Sardo, A. D. S., Becker, C. M., Renner, S. P., Suvitie, P. A., Estadella, J., Vannuccini, S., García-Velasco, J. A., Verguts, J., & Mercorio, A. (2025) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000001027 · Cited by 26 · see citing works
Dienogest Treatment Improves Quality of Life in Women with Endometriosis
Luisi, S. V., Parazzini, F., Angioni, S. L., Arena, S., Berretta, P., Candiani, M., Cela, V., Fedele, L., Litta, P., Maiorana, A., et al. (2015) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.5000232 · Cited by 18 · see citing works
“An empirical dienogest treatment option for women without laparoscopic confirmation represents a suitable adjuvant therapy before undergoing surgery (33).”
BackgroundNew insights on the pathogenesis of endometriosis and novel non-surgical therapies
Suardika, A., & Pemayun, T. G. A. (2018) · Journal of the Turkish-German Gynecological Association · doi:10.4274/jtgga.2018.0090 · Cited by 18 · see citing works
Role of medical treatment of endometriosis
Martone, S., Troìa, L., Marcolongo, P., & Luisi, S. V. (2021) · Minerva Obstetrics and Gynecology · doi:10.23736/s2724-606x.21.04784-5 · Cited by 18 · see citing works
A systematic review and Bayesian analysis of the adverse effects of dienogest
Li, R.-R., Xi, Q., Tao, L., Wei, S., Zhao, C., & Wu, Y. (2024) · BMC Pharmacology and Toxicology · doi:10.1186/s40360-024-00767-1 · Cited by 19 · see citing works
“…have been limited to small retrospective and prospective studies, and few large-scale clinical studies have evaluated the safety of DNG. Strowitzki [21] described the safety profile of dienogest in the European population, but was limited to 4 clinical trials with less homogeneity (a pilot study…”
BackgroundInfluentialGhosh, D., Filaretova, L. P., Bharti, J., Roy, K. K., Sharma, J. B., & Sengupta, J. (2020) · Reproductive Medicine · doi:10.3390/reprodmed1010004 · Cited by 18 · see citing works
Moehner, S., Becker, K., Lange, J. A., von Stockum, S., & Heinemann, K. (2020) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2020.05.049 · Cited by 17 · see citing works
Abesadze, E., Sehouli, J., Mechsner, S., & Chiàntera, V. (2019) · Journal of Minimally Invasive Gynecology · doi:10.1016/j.jmig.2019.08.019 · Cited by 17 · see citing works
Role of Dienogest in Endometriosis in Young Women
Malik, R., & Mann, M. K. (2021) · The Journal of Obstetrics and Gynecology of India · doi:10.1007/s13224-021-01483-0 · Cited by 15 · see citing works
“A long-term 65-week study found that dienogest was well tolerated with side effects like headache, breast discomfort, depressed mood, acne and each of them occurring in less than 10% of the total women [16].”
BackgroundSaglik, B., Selçuki, N. F. T., Aydın, A., Bahat, P. Y., & Akça, A. (2023) · Cureus · doi:10.7759/cureus.34162 · Cited by 15 · see citing works
Update on the management of endometriosis-associated pain in France
Fernandez, H., Agostini, A., Baffet, H., Chabbert‐Buffet, N., Descamps, P., Estrade, J.-P., Giraudet, G., Hocké, C., Salle, B., Trémollières, F., et al. (2023) · Journal of Gynecology Obstetrics and Human Reproduction · doi:10.1016/j.jogoh.2023.102664 · Cited by 16 · see citing works
Kim, H. J., Kim, S. H., Oh, Y. S., Lee, S. R., & Chae, H. D. (2022) · Biomedicines · doi:10.3390/biomedicines10112992 · Cited by 15 · see citing works
Symptom-alleviating effect and adverse effect of dienogest in Korean women with endometriosis
Jeong, S. H., Lee, D., Kim, S. K., & Jee, B. C. (2018) · Gynecological Endocrinology · doi:10.1080/09513590.2018.1469610 · Cited by 12 · see citing works
“of acne, which was higher than the previous study [14].”
ResultTakagi, H., Takakura, M., & Sasagawa, T. (2023) · Taiwanese Journal of Obstetrics and Gynecology · doi:10.1016/j.tjog.2023.08.003 · Cited by 11 · see citing works
Shao, W., Li, Y., & Wang, Y. (2023) · Journal of Ovarian Research · doi:10.1186/s13048-023-01245-8 · Cited by 11 · see citing works
“DNG has good specificity for the progesterone receptor in contrast to dydrogesterone [39], has a direct inhibiting influence on the proliferation of endometrial lesions, and has a stronger cytoreductive impact on endometrial lesions than GnRH-a [46–48].”
BackgroundDel Forno, S., Orsini, B., Verrelli, L., Caroli, M., Aru, A. C., Lenzi, J., Raimondo, D., Arena, A., Borghese, G., Paradisi, R., et al. (2023) · Archives of Gynecology and Obstetrics · doi:10.1007/s00404-023-07125-2 · Cited by 8 · see citing works
Place des nouveaux traitements médicaux dans l’endométriose douloureuse, RPC Endométriose CNGOF-HAS
Legendre, G., Delbos, L., Hudon, E., Chabbert‐Buffet, N., Geoffron, S., Sauvan, M., Fernandez, H., Bouet, P., & Descamps, P. (2018) · Gynécologie Obstétrique Fertilité & Sénologie · doi:10.1016/j.gofs.2018.02.009 · Cited by 9 · see citing works
Long-term clinical outcomes of dienogest for perimenopausal women with symptomatic adenomyosis
Chen, C., Lin, Y.-H., Lee, C., Shen, H., Hsu, Y.-T., & Wu, P.-C. (2025) · Scientific Reports · doi:10.1038/s41598-025-93156-5 · Cited by 9 · see citing works
“…uterine bleeding is the most common side effect, while the other frequently reported adverse effects of DNG, such as headache, acne, nausea, weight gain, breast tenderness, depressed mood, and flatulence, are generally mild-to-moderate and have minimal impact on treatment discontinuation rates 17 .”
Melgaard, A., Vestergaard, C. H., Kesmodel, U. S., Risør, B. W., Forman, A., Zondervan, K. T., Nath, M., Ayansina, D., Saunders, P. T. K., Horne, A. W., et al. (2024) · Human Reproduction · doi:10.1093/humrep/deae273 · Cited by 7 · see citing works
Porto, B. T. D. C., Ribeiro, P. A., Kuteken, F. S., Ohara, F., & Ribeiro, H. S. A. A. (2024) · Women & Health · doi:10.1080/03630242.2024.2382418 · Cited by 11 · see citing works
“Dienogest (DNG), a progestin derivative of 19-nortestosterone, has documented efficacy in alleviating deep endometriosis symptoms (Barra et al. 2020; Strowitzki et al. 2010, 2015).”
Safety of current strategies to manage moderate to severe pain in patients with endometriosis
Ferrero, S., Barra, F., Vatteroni, G., Rosato, F. P., Evangelisti, G., Paudice, M., & Vellone, V. G. (2025) · Expert Opinion on Drug Safety · doi:10.1080/14740338.2025.2547017 · Cited by 7 · see citing works
“A pooled analysis of DNG (2 mg/day) revealed an initial increase in bleeding days, followed by a reduction over time, with amenorrhea rates improving [124].”
Medical treatments of endometriosis: a review
Elbasueny, B., Geerts, M., Yang, E. C., Allaire, C., Yong, P. J., & Bedaiwy, M. A. (2022) · Reproductive and Developmental Medicine · doi:10.1097/rd9.0000000000000053 · Cited by 9 · see citing works
Non-invasive diagnosis and non-surgical treatment of endometriosis: A review
Podzolkova, N. M., Fadeev, I. E., Евгеньевна, М. Е., Poletova, T. N., Вячеславовна, С. Л., & Denisova, T. V. (2022) · GYNECOLOGY · doi:10.26442/20795696.2022.3.201508 · Cited by 7 · see citing works
Geoffron, S., Legendre, G., Daraï, É., & Chabbert‐Buffet, N. (2017) · La Presse Médicale · doi:10.1016/j.lpm.2017.10.005 · Cited by 6 · see citing works
An update on new orally administered contraceptives for women
Nelson, A. L. (2015) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656566.2015.1100173 · Cited by 5 · see citing works
“[31,33] Pooled analysis showed that DNG had been well tolerated with a favorable safety performance over a period of up to 65 weeks.[24] In a related application, studies have shown that DNG may also be effective in the treatment of adenomyosis.”
MethodLong-term treatment of endometriosis with dienogest: Real-world results from the VIPOS study
Moehner, S., Becker, K., Lange, J. A., von Stockum, S., Serrani, M., & Heinemann, K. (2021) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.1177/2284026521993688 · Cited by 4 · see citing works
Dienogest-induced major depressive disorder with suicidal ideation
Lee, S. M., & Park, J. K. (2021) · Medicine · doi:10.1097/md.0000000000027456 · Cited by 5 · see citing works
“Strowitzki et al[10] reported a case of 1 woman who experienced severe depression during a 24-week, randomized, multicenter study with dienogest (2mg/d) in 124 subjects, and the importance of close monitoring for a depression history in these patients was emphasized.”
MethodInfluentialThe challenging role of antiandrogens in the management of polycystic ovary syndrome
Papadimitriou, K., Anagnostis, P. G., & Goulis, D. G. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823045-9.00013-4 · Cited by 5 · see citing works
Evaluation of Dienogest Treatment Efficacy in Patients with Endometriosis
Dobrokhotova, J. E., Ilina, I. Y., Grishin, I. I., Ибрагимова, Д. М., Магомедовна, К. Д., Нариманова, М. Р., Bondarenko, K. R., & Ilchenko, V. J. (2017) · Journal of Endometriosis and Pelvic Pain Disorders · doi:10.5301/je.5000268 · Cited by 5 · see citing works
“Several clinical studies have demonstrated a significant reduction in menstrual blood loss in women who used combined oral contraceptives (COCs) containing dienogest (3, 8-11).”
BackgroundApproaching ovarian endometrioma with medical therapy
Vignali, M., SOLIMA, E., BARBERA, V., BECHERINI, C., & BELLONI, G. M. (2021) · Minerva Obstetrics and Gynecology · doi:10.23736/s2724-606x.20.04751-6 · Cited by 4 · see citing works
Progestins and combined oral contraceptives in the hormonal treatment of endometriosis – a review
Rojek, K. (2023) · European Journal of Clinical and Experimental Medicine · doi:10.15584/ejcem.2023.2.21 · Cited by 5 · see citing works
Lin, S., Wang, X., Fu, X.-L., Yang, W., Wu, H., Bai, Y., Shi, Z.-N., Du, J., & Wang, B.-J. (2021) · World Journal of Meta-Analysis · doi:10.13105/wjma.v9.i4.377 · Cited by 5 · see citing works
Tolerability and Shared Decision-Making in the Hormonal Management of Endometriosis-Associated Pain
Viana, D. P. D. C., Jacobsen, L., Mota, I. L. P., Comin, A., Correia, E. L. D. S., Fernandes, D. D. M., & Dias, A. C. P. (2025) · Biomedicines · doi:10.3390/biomedicines13092294 · Cited by 5 · see citing works
“GnRH analogues are potent and effective but induce a chemical menopause with predictable hypoestrogenic side effects, including significant bone mineral density loss, necessitating the use of add-back therapy for extended treatment [17,27,35].”
Palumbo, M., Giampaolino, P., Pellicano, M., Graziano, V., Bifulco, G., & Corte, L. D. (2026) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2026.2657998 · Cited by 3 · see citing works
“Longitudinal studies extending up to five years confirmed sustained symptom control, low discontinuation rates, and good treatment adherence [2,3,5,6].”
Park, Y., Bae, N., Choo, S. P., Lee, I., Lee, J. H., Kim, Y. J., Cho, S., Choi, Y. S., & Shin, J. (2025) · European Journal of Obstetrics & Gynecology and Reproductive Biology · doi:10.1016/j.ejogrb.2025.114540 · Cited by 2 · see citing works
Dual Targeting of Orphan Nuclear Receptors NR4A1 and NR4A2 for Nonhormonal Endometriosis Therapy
Tsui, W. N. T., Park, Y., Upadhyay, S., Kim, D. M., Zhang, L., Wright, G. A., Hailemariam, A., Oany, A. R., Han, S. J., & Safe, S. H. (2025) · Endocrinology · doi:10.1210/endocr/bqaf144 · Cited by 2 · see citing works
Neues in der Zertifizierung von Endometriosezentren
Schäfer, S. D., Sillem, M., Schweppe, K.-W., Burghaus, S., & Beckmann, M. W. (2021) · Der Gynäkologe · doi:10.1007/s00129-021-04798-1 · Cited by 2 · see citing works
Regression of a Large Endometrioma after Treatment with Dienogest
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“Medical therapy is however often used before surgery to decrease the size of endometriotic implants and the extent of the operation [10].”
BackgroundPotential alternative progestin therapy for low-grade endometrial stromal sarcoma: A case report
Maenohara, S., Fujimoto, T., Okadome, M., et al. (2020) · Gynecologic Oncology Reports · doi:10.1016/j.gore.2020.100634 · Cited by 2 · see citing works
“In fact, long-term trials identified breast discomfort, nausea, and irritability as adverse effects of DNG, whereas thromboembolism was not reported (Strowitzki et al., 2015).”
BackgroundThe role of hormone therapy before hysteroscopic myomectomy
Laganà, A. S., Dababou, S., Bosco, M., Zorzato, P. C., Pomini, P., Paola, R. D., Uccella, S., Raffaelli, R., & Franchi, M. P. (2021) · Clinical and Experimental Obstetrics & Gynecology · doi:10.31083/j.ceog4806200 · Cited by 2 · see citing works
“Numerous clinical studies demonstrated the favorable safety profile of Dienogest [72], as it has been associated with few and tolerable side ef-”
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The issues of endometriosis hormonal treatment in reproductive age women
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Current Status of Clinical Diagnosis and Management of Adolescent Endometriosis
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Efficacy and safety of dienogest versus GnRH-a combined with dienogest therapy for adenomyosisPreprint
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Dienogest in the Treatment of Endometriosis
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“Long-term dienogest showed a favorable safety and tolerability profile, including a low incidence of hypoestrogenic effects and minimal change in bone mineral density [6].”
BackgroundDienogest treatment improves quality of life in women with endometriosis: A prospective cohort study
Arunadevi, V., & Minnalkodi, S. N. S. (2020) · Indian Journal of Obstetrics and Gynecology Research · doi:10.18231/j.ijogr.2020.075
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Diagnostik und Therapie der tief infiltrierenden Endometriose (TIE)
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Prevention of Endometriosis: Is It Possible?
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“The patient complained of adverse effects such as dienogest-like headache, breast discomfort, and depressed mood, as previously reported.(11) Prolonged dienogest therapy is associated with risks and side effects.”
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Get a clear view before starting
Vitale, S. G., Sicilia, G., Fais, M. L., et al. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-21616-9.00021-x
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Clinical Guidance Paper VVOG: Pharmacological treatment of endometriosis-related pain
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“Prolonged use up to 5 years was also found to be safe [26,27].”
Shao, W., Li, Y., & Wang, Y. (2023) · Figshare · doi:10.6084/m9.figshare.23972960
Additional file 4 of A systematic review and Bayesian analysis of the adverse effects of dienogest
Li, R.-R., Xi, Q., Tao, L., Sheng, W., Zhao, C.-C., & Wu, Y.-J. (2024) · Figshare · doi:10.6084/m9.figshare.26756782
Shao, W., Li, Y., & Wang, Y. (2023) · Figshare · doi:10.6084/m9.figshare.23972954
Additional file 2 of A systematic review and Bayesian analysis of the adverse effects of dienogest
Li, R.-R., Xi, Q., Tao, L., Sheng, W., Zhao, C.-C., & Wu, Y.-J. (2024) · Figshare · doi:10.6084/m9.figshare.26756776
- Authors
- Strowitzki, T., Faustmann, T., Gerlinger, C., Schumacher, U., Ahlers, C., & Seitz, C.
- Affiliations
- Heidelberg University (DE)
- Bayer (Germany) (DE)
- Saarland University (DE)
- Jena University Hospital (DE)
- Corresponding author
- Strowitzki, Thomas
- Venue
- International Journal of Women's Health
- Publisher
- Informa UK Limited
- Published
- 2015-04
- Volume
- 7
- Pages
- 393
- ISSN
- 1179-1411 (ISSN-L)
- PMC
- PMC4403681
- OpenAlex
- W2079421112
- Semantic Scholar
- 539bf4cea6fa64b6ec191b7f1182b7cd380b9456
- Cited by
- 120
- References
- 44
- Citations by year
- 2026: 11 · 2025: 8 · 2024: 8 · 2023: 23 · 2022: 11 · 2021: 15 · 2020: 12 · 2019: 2 · 2018: 11 · 2017: 9 · 2016: 6 · 2015: 4
- FWCI
- 11.41
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Women s Health (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Endometriosis Research and Treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ectopic Pregnancy Diagnosis and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Menstrual Health and Disorders
- Keywords
- dienogest, endometriosis, drug safety, tolerability, adverse drug reactions, bleeding patterns, estradiol levels, long-term treatment, headache, breast discomfort, acne, lesion reduction, pain intensity
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