Review of Long Term Effects of Oral Contraceptive Pill Ncbi 2019

• Journal List
• Contracept X
• five.i; 2019
• PMC7286154

Contracept 10. 2019; 1: 100002.

Continuous vs. cyclic combined hormonal contraceptives for treatment of dysmenorrhea: a systematic review ^{☆ ☆☆}

Tiffany Damm

^aUniversity of Key Florida Higher of Medicine, Orlando, FL

Georgine Lamvu

^aUniversity of Fundamental Florida College of Medicine, Orlando, FL

^bSectionalisation of surgery, Gynecology section, University of Cardinal Florida College of Medicine and Orlando VA Medical Center, Orlando, FL

Jorge Carrillo

^aAcademy of Cardinal Florida College of Medicine, Orlando, FL

^bDivision of surgery, Gynecology department, University of Central Florida Higher of Medicine and Orlando VA Medical Eye, Orlando, FL

Chensi Ouyang

^bSectionalization of surgery, Gynecology department, University of Central Florida College of Medicine and Orlando VA Medical Center, Orlando, FL

^cGraduate Medical Educational activity, Fellowship in Advanced Minimally Invasive Gynecology, Florida Hospital, Orlando, FL

Jessica Feranec

^aUniversity of Key Florida Higher of Medicine, Orlando, FL

^bDivision of surgery, Gynecology section, University of Primal Florida College of Medicine and Orlando VA Medical Center, Orlando, FL

Received 2018 Jun 28; Revised 2019 Jan fourteen; Accustomed 2019 Jan sixteen.

Abstract

Objective

This systematic review aims to evaluate the benefits of oral continuous combined hormonal contraceptives (CHCs) in managing dysmenorrhea by comparison randomized controlled trials (RCTs) evaluating the efficacy of continuous vs. cyclic CHC utilize for the following outcomes: (a) reducing dysmenorrhea duration and frequency, (b) severity, (c) recurrence and (d) interference with daily activity.

Report blueprint

Cochrane, PUBMED and Popline databases were searched from 1934 to 2018 for all relevant studies evaluating CHC for handling of dysmenorrhea. A study was selected if it (a) compared continuous regimen vs. cyclic regimen of oral CHC, (b) measured dysmenorrhea as a master or secondary outcome, (c) was an RCT and (d) was published in English. Due to differences in CHC used and result measurement, a systematic analysis of private study results and a limited meta-analysis were conducted.

Results

Of 780 studies that were screened by title and abstract, viii were included in the final assay; 6 evaluated cyclic vs. continuous CHC, and ii evaluated cyclic vs. extended/flexible CHC use. Quality of prove was low for all event measures. Overall, compared to circadian use, flexible/extended CHC resulted in four fewer days of dysmenorrhea. Studies revealed conflicting results for interference with daily action, hurting severity and pain recurrence. Side furnishings were few in both comparison groups.

Conclusions

Continuous or extended/flexible CHC utilize may reduce dysmenorrhea duration compared to circadian regimen; however, more rigorous inquiry is needed.

Implications

This systematic review shows that continuous CHC use may reduce dysmenorrhea elapsing compared to cyclic regimen, although the quality of evidence is depression. Hereafter double-blinded RCTs with more than rigorous study blueprint, consistent outcome measures and comprehensive upshot reporting are needed.

Keywords: Dysmenorrhea, Oral contraceptives, Hormonal contraceptives, Treatment

ane. Introduction

Dysmenorrhea is defined as cyclic crampy lower abdominal or pelvic hurting that occurs just earlier and/or during menstruation, affecting approximately l%–90% of reproductive age women worldwide [i], [2], [3], [iv]. Primary dysmenorrhea does non have discernable macroscopic pathology, while secondary dysmenorrhea results from diseases such as endometriosis, adenomyosis or uterine fibroids [five]. Dysmenorrhea pain scores are moderate in 37%–47% and severe in 17%–xviii% of women [6], [seven], and dysmenorrhea is associated with decreased quality of life, depression and anxiety [v], [8], [nine], [10].

In contempo studies, women with dysmenorrhea demonstrate functional and structural changes in the areas of the brain responsible for pain processing, like women with noncyclic chronic pelvic pain due to endometriosis [11], [12]. Initial longitudinal studies suggest that central changes associated with chronic hurting may be reversible once the nociceptive input is removed. Researchers speculate that untreated dysmenorrhea may increase the adventure of developing chronic pelvic pain and associated comorbidities [5] and that early screening and treatment of dysmenorrhea may prevent women from developing chronic pelvic pain.

Cyclic combined hormonal contraceptives (CHCs) are commonly used as 2d-line therapy for dysmenorrhea, following first-line therapy of nonsteroidal anti-inflammatory drugs [xiii], [14], [15]. CHCs may be prescribed as continuous, extended or flexible regimens. Cyclic apply consists of 21 days of active hormone tablets followed past a vii-day hormone-free interval during which the patient experiences withdrawal bleeding. Continuous regimens skip the hormone-gratis interval to eliminate menstruation. Extended regimens lengthen the interval of active hormone to greater than 21 days, resulting in decreased and delayed menstruation. Flexible regimens allow women to initiate a hormone-gratis interval at their discretion, ordinarily in response to unscheduled or "quantum" bleeding.

CHCs have been shown in randomized controlled trials (RCTs) to be similarly effective when used in circadian, continuous, extended or flexible regimens for contraception [xvi]. A Cochrane systematic review of ten studies confirmed that circadian CHCs as well significantly improve dysmenorrhea [15]. Continuous/extended regimen contraceptives are part of American Higher of Obstetricians and Gynecologists dysmenorrhea direction guidelines [17]. However, their efficacy in the handling of dysmenorrhea has not been studied in a systematic fashion.

Our research goal is to draw the existing evidence gap and systematically review all relevant RCTs evaluating the efficacy of continuous/flexible vs. cyclic CHC for the management of dysmenorrhea.

2. Materials and methods

2.1. Search strategy

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines [18]. The research question was defined a priori. Three databases — Popline, Cochrane and PUBMED — were queried. We searched Popline using keywords dysmenorrhea and contraception, Cochrane for reviews comparing continuous vs. cyclic contraception and dysmenorrhea, and the PUBMED computerized database from 1934 to 2018 (last searched on September 23,2018) using the following search strategy of Keywords: (oral contracept* OR hormonal contracept* OR combined contracept*) AND (menstrual hurting[tw] OR pelvic hurting[tw] OR dysmenorrhea OR dysmenorrhea) AND (flexible OR extended OR cyclic OR cyclical OR continuous).

2.2. Selection criteria

Articles were included in this review if they were RCTs that (a) compared continuous or extended vs. cyclic CHC and (b) measured dysmenorrhea as a primary or secondary upshot. We excluded studies not published in English language. The population of involvement was any reproductive age woman desiring contraception. The post-obit dysmenorrhea outcomes were reviewed: (a) duration, (b) frequency, (c) severity, (d) recurrence, (e) days when dysmenorrhea interfered with activity and (f) side effects and agin effects.

2.3. Study pick, data synthesis and quality of evidence assessment

The principal reviewer (T.D.) evaluated titles and abstracts identified from the literature search of Cochrane, PUBMED and Popline to determine papers requiring total-text review every bit per the inclusion and exclusion criteria. Two authors (T.D. and C.O.) independently evaluated the included studies for risk of bias and quality of evidence according to the Course Handbook [19] using Review Manager 5 (RevMan 2014) [20] and GRADEpro [21], with reviewer G.L. serving as adjudicator. Factors that were considered when evaluating take a chance of bias included random sequence generation, allocation concealment, blinding, incomplete outcome reporting and selective reporting. Evidence quality for each outcome was rated as high, moderate, depression or very low based on cess of the studies' hazard of bias, inconsistency, indirectness, imprecision and publication bias. Due to the differences in blazon of contraceptive used and method of upshot measurements in each study, only limited meta-analysis was performed, and the outcomes of studies not included in the meta-analysis are reported in narrative form.

3. Results

A total of 794 articles were extracted from Cochrane, PUBMED and Popline search. After removal of duplicates, 780 studies were screened for eligibility (Fig. 1). Of the xv articles that were assessed for eligibility past total text, seven were excluded for the following reasons: not a randomized control trial [22], [23], [24], [25], [26], control group was using placebo [27] and continuous intervention was using progestin just [28]. From the eight studies included in descriptive analysis, two had similar methodology and were evaluated in a meta-analysis [35], [36]. All eight studies in the final analysis were RCTs published between 2002 and 2017. Circadian regimen consisted of 21 days of active hormone with a 7-solar day hormone-free interval unless otherwise divers.

Flowchart of study selection.

Characteristics of studies are summarized in Table 1. Study elapsing ranged from 6 to 24 months. Study locations spanned 7 countries. V types of progestins were used across studies. Hazard of bias for each outcome is represented in Fig. two. Overall, all studies had serious risk of bias. Ii studies had unknown random sequence generation [29], [36]. Four studies had unknown allocation concealment [29], [31], [33], [36]. Vii studies had unknown blinding or were open label [29], [31], [32], [33], [34], [35], [36]. Incomplete outcome bookkeeping occurred in two studies [33], [36]. Selective reporting occurred in one study [32]. Summary of evidence evaluating quality of evidence and effect of intervention for each outcome is presented in Table 2. Quality of evidence was (a) depression for duration, (b) very low for frequency, (c) very low for severity, (d) low for recurrence charge per unit and (due east) low for days with dysmenorrhea interfering with daily action.

Table i

Characteristics of studies

Written report	Location	Design	Study duration	Medical intervention	Type of OCP	Mean age (Due south.D.)	Number of patients	Outcomes and time points measured
Kwiecien 2002	USA	RCT	6 months	CYC: 21/7 days CON: 168 days	20 mcg EE/0.1 mg levonorgestrel	CYC: 26.5 (4.five) CON: 29.3 (six.7)	CYC: 16 CON: 16	Number of days with dysmenorrhea measured over 6 months.
Legro 2008	United states	RCT	6 months	CYC: 21/seven days CON: 168 days	twenty mcg EE/1 mg norethindrone	CYC: 27.5 (4.seven) CON: 26.9 (5.6)	CYC: 31 CON: 31	MMDQ (cyclical perimenstrual symptoms including dysmenorrhea) measured at baseline and over again at half dozen months.
Seracchioli 2010	Italian republic	RCT	24 months	CYC: 21/7 days CON: 730 days	20 mcg EE/0.075 mg gestodene	CYC: 30.2 (two.four) CON: 29.six (two.vii)	CYC: 92 CON: 95	Dysmenorrhea recurrence rate defined every bit VAS > iv out of ten-betoken scale and modify in severity of dysmenorrhea (10-point VAS scale) later on endometrioma excision, measured at 6, 12, xviii and 24 months.
Machado 2010	Brazil	RCT	half dozen months	CYC: 21/7 days CON: 168 days	30 mcg EE/iii mg drospirenone	CYC: 27.7 (5.1) CON: 27.9 (4.iv)	CYC: 39 CON: 39	Change in percent of women experiencing dysmenorrhea recorded past patient diary at i and 6 months.
Muzii 2011	Italy	RCT	6 months	CYC: 21/vii days CON: 168 days	20 mcg EE/0.15 mg desogestrel	CYC: thirty.iii (two.ix) CON: thirty.half-dozen (iii.1)	CYC: 28 CON: 29	Dysmenorrhea recurrence charge per unit defined as VAS > 4 out of 10-point scale and change in severity of dysmenorrhea (10-betoken VAS scale) later endometrioma excision, measured at 3, vi, 12 and 24 months.
Dmitrovic 2012	Croatia	RCT	half-dozen months	CYC: 21/7 days CON: 168 days	20 mcg EE/0.075 mg gestodene	CYC: 21.1 (4.three) CON: 20.7 (iii.9)	CYC: 19 CON: xix	Reduction in dysmenorrhea equally measured by 100-mm VAS scale and dysmenorrhea severity as assessed by MMDQ at 1, 3 and 6 months.
Strowitzki 2012	UK and Federal republic of germany	RCT	140 days	CYC: 24/4 days FLEX: upward to 140 days	20 mcg EE/3 mg drospirenone	CYC: 25.3 (5.0) FLEX: 25.six (v.1)	CYC: 108 FLEX: 115	Numbers of days with dysmenorrhea and days in which dysmenorrhea interfered with daily activities as measured past patient diary for 140 days.
Momoeda 2017	Nippon	RCT	364 days	CYC: 24/iv days FLEX: up to 364 days	xx mcg EE/3 mg drospirenone	CYC: 30.4 (half dozen.half dozen) FLEX: 28.9 (six.0)	CYC: 107 FLEX: 105	Numbers of days with dysmenorrhea and days in which dysmenorrhea interfered with daily activities as measured by patient diary for 364 days. Pain severity reduction was measured by a 100-mm VAS scale over 364 days.

Tabular array 2

Summary of bear witness

Certainty assessment							No. of patients		Effect		Certainty
No. of studies	Written report pattern	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Continuous oral combined contraception	Cyclic oral combined contraception	Relative (95% CI)	Absolute (95% CI)
Dysmenorrhea duration (follow-up: median 140 days; assessed with: daily periodical)
3	Randomized trials	Seriousa	Not serious	Seriousb	Not serious	None	236	231	-	Physician 4.0 days lower (5.7 lower to 2.iii lower)k	⨁⨁◯◯ Low
Dysmenorrhea frequency (follow-up: mean 168 days; assessed with: daily journal)
ane	Randomized trials	Seriousc	Not serious	Seriousd	Seriouse	None	Continuous and cyclic regimen each included 39 women. Frequency was measured as the percentage of women with dysmenorrhea after the 1st and 6th pill pack. Frequency declined from 59% to 28.2% (p <.02) in the continuous regimen group and from 44.4% to 27.8% in the cyclic regimen (noted equally not statistically significant just p value not reported). Based on the available testify, we are uncertain whether there is any difference in dysmenorrhea frequency among patients taking either cyclic or continuous CHC.				⨁◯◯◯ Very low
Dysmenorrhea severity (follow-up: range 1 months to 6 months; assessed with: ten-point VAS scale, 100-mm VAS scale, MMDQ)
5	Randomized trials	Seriousf	Not serious	Very seriousk	Not serious	None	There were 277 women in the cyclic and 279 continuous group. Studies differed in measurement of pain severity, report duration and progestins used. Dmitrovic 2012 and Legro 2008 both measured severity using the MMDQ. Dmitrovic 2012 reported no difference in MMDQ pain score, mean departure 4.5 (95% CI − 22.2 to 13.two, p =.6). Legro 2008 reported a mean difference of eight.iv (95% CI 2.0–14.vii, p =.01) at 6 months, favoring continuous CHC. Seracchioli 2010 reported median divergence of two on 10-indicate VAS scores at 6 months (p <.0005), favoring continuous CHC. Muzii 2011 too evaluated pain severity on 10-betoken VAS only found no meaning divergence (no numerical data were provided). Momoeda 2017 and Dmitrovic 2012 evaluated pain severity using 100-mm VAS. Momoeda 2017 reported that there was no meaning difference in pain reduction over half dozen months (no numerical data were provided). Dmitrovic 2012 reported a mean difference in favor of continuous CHC at 1 calendar month of − 27.iii (95% CI − 40.5 to − 14.two, p <.001) and at three months of − 17.8 (95% CI − 33.four to − 2.1, p =.03); withal, the authors noted no difference in dysmenorrhea severity at half-dozen months, − 16.0 (95% CI − 32.2 to 0.1, p =.05). Based on the available bear witness, we are uncertain whether there is any departure in dysmenorrhea severity amongst patients taking either cyclic or continuous CHC.				⨁◯◯◯ Very low
Dysmenorrhea recurrence (follow-upwardly: range 6 months to 48 months; assessed with: 10-signal VAS)
2	Randomized trials	Serioush	Not serious	Seriousi	Not serious	None	At that place were a full of 120 women in the cyclic regimen and 124 in the continuous regimen. Recurrence rates were defined as hurting severity VAS > 4 during handling. Seracchioli 2010 showed that, after 24 months of treatment, recurrence rates were < 5% in the continuous regimen compared to 25%–30% in the cyclic regimen (p <.005). Muzii 2011 showed that, after 12 months of treatment, recurrence rates were 17% in the continuous regimen compared to 32% in the continuous regimen (p =.54). Based on the bachelor prove, we are uncertain if in that location is any difference in dysmenorrhea recurrence among patients taking either cyclic or continuous CHC.				⨁⨁◯◯ Low
Numbers of days when dysmenorrhea interfered with daily action (follow-up: range 140 days to 168 days; assessed with: daily journal)
ii	Randomized trials	Seriousj	Not serious	Not serious	Seriouseast	None	There were a full of 215 women in the circadian regimen and 220 in the flexible regimen. Strowitzki 2012 reported a mean difference of 2.2 fewer days (95% CI − 4.ii to − 0.1) in favor of flexible regimen, and Momoeda 2017 reported 2.0 days fewer (95% CI − seven.5 to 3.5), not statistically significant. Standard deviations non reported past studies; therefore, we were unable to compile meta-analysis. Based on the bachelor evidence, we are uncertain if there is any deviation in number of days with dysmenorrhea that interfered with daily activities among patients taking either cyclic or flexible CHC.				⨁⨁◯◯ Low
Side effects
5	Randomized trials	-	-	-	-	-	All studies reported side effect profiles except for Seracchioli 2010 and Muzii 2011. Types of side effects assessed varied among studies. Kwiecien 2002 reported decrease of bloating in the continuous group, with a mean difference of x.4 days less (p =.04). Machado 2010 establish that there was a significant decrease of headache (p <.02), nausea (p <.02), appetite (p <.05) and acne (p <.05) in the continuous compared to circadian group. Notwithstanding, Momoeda 2017, Strowitzki 2012 and Kwiecien 2002 found no difference in headaches, nausea or airsickness, and Legro 2008 also reported no difference in nausea and airsickness. Dmitrovic 2012 constitute greater weight proceeds in the continuous group (mean difference 2.three kg, 95% CI 0.eight–three.8, p =.003) and subtract in systolic claret force per unit area (p <.05); notwithstanding, no differences were reported by Legro 2008, Machado 2010 or Strowitzki 2012. Legro 2008, Dmitrovic 2012 and Strowitzki 2012 found no departure in triglycerides, LDL and full cholesterol. While Legro 2008 found an increase in serum HDL-C in the cyclic grouping, (mean difference 5.0, 95% CI 0.7–9.3, p =.02), neither Dmitrovic 2012 and Strowitzki 2012 found a difference.				-

Kwiecien et al. [29] studied 32 women who were evenly randomized to receive either 168 days of circadian or continuous regimen of 20 mcg ethinyl estradiol/0.1 mg levonorgestrel. One of the study's secondary outcome was number of days with dysmenorrhea. Patients taking continuous CHC had fewer days with dysmenorrhea than those taking cyclic CHC (ane.nine vs. 13.3 days, p <.01).

Legro et al. [30] studied 62 women, evenly randomized to receive 20 mcg ethinyl estradiol/1 mg norethindrone in either a circadian or continuous regimen for 168 days. Dysmenorrhea was a secondary event and was assessed using the Moos-Menstrual Distress Questionnaire (MMDQ) administered at baseline and one time per menstrual wheel thereafter. The change in dysmenorrhea severity during handling compared to baseline was greater (p =.010) in the continuous group (− 5.8) vs. the cyclic group (2.6).

Seracchioli et al. [31] studied women with secondary dysmenorrhea from endometriosis who had undergone laparoscopic excision of symptomatic ovarian endometrioma. After surgery, they were randomly assigned to i of three groups: (a) no additional treatment (104 allocated and 87 completed the trial), (b) cyclic oral CHC (103 allocated and 92 completed the trial) and (c) received continuous oral CHC (104 allocated and 95 completed the trial). Participants used 0.020 mg ethinyl estradiol/0.075 mg gestodene for 24 months. The primary outcome, dysmenorrhea recurrence [divers as ten-point Visual Analogue Scale (VAS) score ≥ 4], decreased in the continuous CHC grouping compared to cyclic CHC and placebo groups (p <.005).

Machado et al. [32] studied 78 women evenly randomized to a cyclic regimen or continuous regimen using xxx mcg ethinyl estradiol/3 mg drosperinone for 168 days. Twenty-nine women in each group (74%) successfully completed the trial. Frequency of dysmenorrhea was a secondary outcome. There was a subtract in dysmenorrhea frequency from 59% at i calendar month to 29% at half dozen months among the women taking continuous regimen (p <.02). No statistical deviation was institute for the cyclic group (44% at i months to 28% at six months).

Muzii et al. [33] studied participants who were previously diagnosed with endometriomas larger than 3 cm, had moderate to severe dysmenorrhea or chronic pelvic hurting (≥ iv on a 10-point VAS calibration) and had not used estroprogestins in the terminal 6 months. All women underwent laparoscopic excision of ovarian endometriomas. 20-8 women postoperatively received 20 mcg ethinyl estradiol/0.15 mg desogestrel in a circadian regimen, and 29 women received continuous active hormone for 168 days. One of the primary outcomes of the study was hurting recurrence divers as dysmenorrhea or chronic pain that was graded ≥ 4 on the ten-point VAS scale. There was no significant difference in pain recurrence rate between the continuous and the circadian groups (17% vs. 32%, p =.54). The discontinuation rate was significantly increased in the continuous group (41% vs. 14% in the circadian regimen, p =.03) and was mainly attributed to breakthrough bleeding. Six women who discontinued the continuous regimen were crossed over to the cyclic regimen, and the other six discontinued all hormonal treatments. The four patients who did not complete the cyclic regimen were observed without farther treatment.

Dmitrovic et al. [34] studied 38 women with history of primary dysmenorrhea (onset < iii years after menarche) and three months of moderate to severe primary dysmenorrhea prior to enrollment, and used 0.075 mg gestodene and 20 mcg ethinyl estradiol every bit either cyclic or continuous regimen for 168 days. Fourteen women in the cyclic group and 15 in the continuous group completed the study. Pain severity, the primary outcome, was measured using 100-mm VAS and the MMDQ over half dozen months. In that location was no deviation in MMDQ hurting score, hateful difference 4.5 [95% conviction interval (CI) − 22.two to 13.2, p =.61]. There was a hateful difference in favor of continuous CHC at 1 month, − 27.iii (95% CI − 40.five to − 14.2, p <.001), and at 3 months, − 17.8 (95% CI − 33.4 to − 2.i, p =.03). Withal, there was no departure in dysmenorrhea severity at 6 months, − 16.0 (95% CI − 32.2 to 0.1, p =.05).

Strowitzki et al. [35] studied participants with moderate to severe primary dysmenorrhea in at to the lowest degree iv of 6 preceding menses and used 20 mcg ethinyl estradiol/three mg drosperinone. There were 108 women in the cyclic group (24 days active tablets/3 days hormone-free tablets) and 115 women in the extended/flexible grouping, where women could employ the CHC for as long as they desired until they experienced 3 days of consecutive bleeding. At that signal, participants started a iv-day hormone-free period before resuming agile tablets. Of the 223 participants, 210 women completed the trial (110 in the extended regimen and 100 in the cyclic regimen). The principal effect was the number of days with dysmenorrhea. The investigators found that women in the extended/flexible regimen spent fewer days with dysmenorrhea (− 4.two days, 95% CI − 6.v to − 2.0, p <.001) and with dysmenorrhea that interfered with daily activities (− two.ii days, 95% CI − iv.2 to − 0.ane) when compared to women on the cyclic regimen.

Momoeda et al. [36] studied women with dysmenorrhea baseline score of ≥ iii points in 2 prior consecutive menstruum and used extended/flexible vs. circadian CHC (twenty mcg ethinyl estradiol/three mg drospirenone). A full of 216 patients were evenly randomized into the two groups. Women in the flexible regimen used CHC ≥ 24 days and up to 120 days. Later on 3 sequent days of bleeding, patients started a four-day hormone-free interval prior to resuming CHC. Women in the cyclic regimen received 24 days of active tablets and 4 days of hormone-free tablets. Ninety-eight participants (91%) in the flexible/extended group and 84 participants (78%) in the cyclic group completed the 168-day written report. Of the 98 women in the flexible/extended group, 59 continued with long-term follow-up for a total of 364 days. The primary event was defined as number of days with at least mild dysmenorrhea. Women using the flexible/extended regimen reported 3.four fewer days of dysmenorrhea when compared to women using the cyclic regimen (95% CI − 6.5 to − 0.three, p =.030). There was no departure in the number of days with dysmenorrhea that interfered with daily activeness (mean difference 2.0, 95% CI − 7.5 to three.v). Both the flexible/extended regimen and the circadian regimen were associated with a decrease in dysmenorrhea severity from baseline; yet, no statistical divergence was institute. Later 364 days of flexible/extended regimen, there was no statistical difference in the reduction in dysmenorrhea severity when compared to 168 days of treatment.

Meta-assay was performed for 2 studies: Momoeda et al. and Strowitzki et al. [35], [36]. The analysis showed that women who used the flexible/extended regimen reported 3.98 fewer days of dysmenorrhea (95% CI − v.69 to − two.27) when compared to women using the cyclic regimen (Fig. 3). The other studies had unlike methods of event measurements, were using different progestin formulations of CHC or did not publish sufficient data to be compiled into a meta-analysis.

Due to the very low quality of bear witness, we are uncertain whether there is any deviation in dysmenorrhea frequency and severity among patients taking either circadian or continuous CHC. Due to the conflicting results from bachelor prove, nosotros are uncertain if in that location is any divergence in dysmenorrhea or in the number of days with dysmenorrhea that interfered with activities amid patients taking either circadian or continuous/flexible CHC.

The number of adverse events reported past studies was low and comparable between groups. Several studies measured various side effects. Kwiecien et al. [29] reported decrease of bloating in the continuous group, with a mean departure of x.4 days less (p =.04). Machado et al. [32] found that at that place was a significant subtract of headache (p <.02), nausea (p <.020), appetite (p <.05) and acne (p <.05) in the continuous compared to the circadian grouping. However, others found no meaning difference in headaches, nausea or vomiting [27], [28], [33], [34]. Dmitrovic et al. [34] found greater weight gain in the continuous grouping (mean difference 2.iii kg, 95% CI 0.8–3.8, p =.003) and decrease in systolic claret pressure (p <.050); notwithstanding, again, no differences were reported past others [30, 32, 36]. No significant difference was found in triglycerides, low-density lipoprotein (LDL) and total cholesterol [30], [34], [36]. While Legro et al. [30] found an increase in serum high-density lipoprotein cholesterol (HDL-C) in the cyclic group (mean difference 5.0, 95% CI 0.seven–nine.three, p =.02), neither Dmitrovic et al. [34] and Strowitzki et al. [36] reported a difference.

4. Word

CHCs are routinely used in a multifariousness of regimens for contraception. Although both cyclic and continuous regimens are recommended for treatment of dysmenorrhea [37], there has not been a systematic review comparing the efficacy of the different regimens. Our research suggests that continuous and flexible CHC may result in 4 days less spent in pain when compared to cyclic CHC. Nosotros are uncertain whether continuous and flexible CHC decreases dysmenorrhea severity, frequency, recurrence and days when dysmenorrhea interferes with activeness due to the very low quality of evidence or alien evidence. Side effects and adverse events were few, and there is not enough high-quality evidence about differences in side effects that can be attributed to cyclic vs. continuous or flexible CHC.

Although our findings are based on RCTs, at that place are several limitations. Well-nigh all trials used different formulations of CHC and measured outcomes using different scales, which limited our ability to perform a large meta-analysis. Our written report examined CHC just and did not include the many formulations of progestin-only contraceptive. During our literature review, nosotros did find some studies examining progestin-only contraceptives, and farther research regarding their efficacy on dysmenorrhea would be valuable. Study populations were heterogeneous, with eight RCTs conducted in 3 different continents, which might account for conflicting results regarding dysmenorrhea severity. Only English studies were reviewed, further limiting generalizability. Quality of evidence was low for three outcomes (duration, severity and days when dysmenorrhea interfered with activity) and was very low for dysmenorrhea recurrence and frequency. Attrition bias was a business in two studies. Bulk of studies were either open label or had unclear blinding, and several had unclear allocation concealment, leading to an increment in risk of bias. More high-quality double-blind RCTs are needed to address these limitations. Lastly, the number of participants enrolled in each written report was small. However, there were a total of 889 patients when all studies were combined, and the optimal information size criteria were met in all outcomes except for days when dysmenorrhea interfered with daily activity and dysmenorrhea frequency.

In conclusion, our findings propose that continuous or flexible CHC may exist more effective than cyclic CHC in decreasing dysmenorrhea duration without increasing side furnishings or adverse events. Given the recent show suggesting that untreated dysmenorrhea may increase the chance for developing chronic pelvic hurting and long-standing psychiatric dysfunction [five], it is important that high-quality research is conducted to more confidently elucidate the effect of continuous CHC on dysmenorrhea.

Acknowledgments

We would similar to give thanks Shalu Gillum, J.D., K.L.S., AHIP, for her assistance with query of the literature databases.

Footnotes

^☆Disclosures: Dr. Chensi Ouyang, Dr. Georgine Lamvu, Dr. Jorge Carrillo and Dr. Jessica Feranec are employees of the Veterans Affairs Medical Center in Orlando, Florida. Dr. Georgine Lamvu serves as Chairman of the Board for the International Pelvic Hurting Society. In 2017, she served on the Obstetrics and Gynecology Advisory Board for Daiichi Sankyo Inc. and as a consultant for Abbvie Pharmaceuticals and Uroshape Inc. Additionally, Dr. Lamvu has inquiry funding from Pfizer, Grants for Learning and Change and the National Vulvodynia Association.

^☆☆Funding: none.

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Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286154/

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