Network meta-analysis

Regular menstrual cycles

Polycystic ovary syndrome

weeks 12 to 52 (target week 26)Not stated by the trialsDoses of a drug pooledOdds ratio

Randomized trials

Treatments

173

Participants

136

Events

In plain language

Across 3 trials with 173 participants, 0 of 3 treatments had a clearly better result than standard care or no added treatment on regular menstrual cycles, and for 3 the evidence could not tell them apart from standard care or no added treatment. The most favorable estimate was for Semaglutide injection: odds ratio 3.27 (95% credible interval 0.72 to 14.84).

Higher values favor the treatment. "Clearly" means the 95% credible interval excludes no difference. These are averages across trials; they do not say how any one person will respond. Not medical advice.

Network of trials

Each circle is a treatment; each line joins treatments that were randomized against each other in at least one trial.

Node area shows participants; line width shows trials comparing two treatments directly. Blue: GLP-1 receptor agonist containing treatments; grey: comparators. Hover over or tab to a node or line for details.

Effects compared with Standard care or no added treatment

Odds ratio. Higher values favor the treatment.

Versus Standard care or no added treatment, log scale. Blue: Bayesian random effects posterior median with 95% credible interval (thick) and 95% prediction interval (dashed). Amber diamond: frequentist estimate with 95% confidence interval. Hover over or tab to a row for its values.

Effects of each treatment versus Standard care or no added treatment
Treatment	Bayesian OR (95% CrI)	95% prediction interval	Frequentist OR (95% CI)	Verdict
Semaglutide injection SEMA_SC	3.27 (0.72 to 14.84)	0.50 to 19.44	3.47 (1.04 to 11.56)	Unclear
Cyproterone ethinylestradiol OTHER_ACTIVE_cyproterone_ethinylestradiol	1.76 (0.19 to 15.44)	0.15 to 18.64	2.04 (0.22 to 18.63)	Unclear
Liraglutide injection LIRA_SC	1.52 (0.25 to 9.64)	0.19 to 12.11	1.70 (0.26 to 11.16)	Unclear

Ranking

How likely each treatment is to be among the best. Rankings ignore the size of differences and their certainty, so read them with the effects above.

League table

Every treatment against every other: odds ratio of the row treatment versus the column treatment, posterior median and 95% credible interval. Green: row clearly better; red: row clearly worse.

Every treatment in a row compared with every treatment in a column
Row versus column	STANDARD_CARE	SEMA_SC	OTHER_ACTIVE_cyproterone_ethinylestradiol	LIRA_SC
STANDARD_CARE	STANDARD_CARE	0.31 0.07 to 1.38	0.57 0.06 to 5.19	0.66 0.10 to 3.96
SEMA_SC	3.27 0.72 to 14.84	SEMA_SC	1.86 0.14 to 26.51	2.08 0.21 to 22.79
OTHER_ACTIVE_cyproterone_ethinylestradiol	1.76 0.19 to 15.44	0.54 0.04 to 7.38	OTHER_ACTIVE_cyproterone_ethinylestradiol	1.14 0.25 to 5.33
LIRA_SC	1.52 0.25 to 9.64	0.48 0.04 to 4.78	0.88 0.19 to 4.06	LIRA_SC

Heterogeneity, fit and convergence

Bayesian random effects (primary)

Heterogeneity (tau): 0.338 (95% CrI 0.079 to 1.265), log scale
Residual deviance: 5.8 for 6 data points
DIC: 11.6 (pD 5.8)
Largest R-hat: 1.001
Smallest ESS: bulk 3,916, tail 4,646
Divergent transitions: 0
Convergence: All criteria met
Priors: PR02 N(0, 5^2); PR05 N(0, 2.5^2); PR09 log normal(-2.06, 1.51^2) on tau^2 (Signs/symptoms reflecting continuation/end of condition, pharm vs placebo control)

Frequentist check (netmeta)

Method: inverse variance, REML, OR
Tau: 0.000
Q (total): 0.00 on 0 df
Q (between designs): 0.00

Inconsistency

Do trials comparing two treatments directly agree with the indirect evidence through other treatments?

No comparison here has both direct and indirect evidence, so inconsistency cannot be checked by node splitting; the between designs Q above is the global check.

Small study effects

A comparison adjusted funnel plot: each point is one trial comparison, centered on its own network estimate. Asymmetry can signal that small trials with unfavorable results are missing.

Fewer than ten trial comparisons, too few to judge funnel plot asymmetry.

Comparability of the trials

Checked across designs (the set of treatments each trial compares) for eligibility, outcome definition and assessment, and the baseline factors above. Flags point to possible intransitivity; notes describe variation that is not tied to design.

FlagOutcome assessment, definition: confounded with design: dominant follicle on ultrasound, called ovulation in the abstract 1, established a regular menstrual cycle 1, recurrence of regular menstrual cycles 1
NoteOutcome assessment, time point: selected time points span 12 to 20 weeks

Comparability items per trial
Trial	time weeks	analysis set	definition	instrument	adjudicated	proportion method	intercurrent events (discontinuation)	intercurrent events (rescue)	blinding	funding	start year	Eligibility
NCT04969627	12	completers	recurrence of regular menstrual cycles	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2021	age 18 to 40; Rotterdam PCOS phenotype B; BMI 24 or more
NCT03151005	12	completers	dominant follicle on ultrasound, called ovulation in the abstract	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2017	Rotterdam PCOS, BMI 24 kg/m2 or more, age 18 to 50 years
S003422	20	completers	established a regular menstrual cycle	not stated	not stated	not stated	not stated	not stated	open_label	non_industry	2023	women with infertility and PCOS by Rotterdam criteria; BMI 24 or higher; no diabetes

Trial data

What each trial contributes. Arm rows give the arm value with its standard error, or events over participants; contrast rows give the odds ratio on the analysis scale (log) against the trial's first row. Flags mark converted, combined or approximated inputs.

Trial data entering this analysis
Trial	Arm	Treatment	Week	Data	Events / N	Source
NCT04969627	A1	STANDARD_CARE	12	arm, responders	22 / 25	R0025102:Table 2
NCT04969627	A2	LIRA_SC	12	arm, responders	25 / 27	R0025102:Table 2
NCT03151005	A1	OTHER_ACTIVE_cyproterone_ethinylestradiol	12	arm, responders	23 / 30	R0007146:Table 1
NCT03151005	A2	LIRA_SC	12	arm, responders	22 / 30	R0007146:Table 1
S003422	A1	STANDARD_CARE	20	arm, responders	18 / 30	R0046339:Table 3
S003422	A2	SEMA_SC	20	arm, responders	26 / 31	R0046339:Table 3

Rerun this analysis yourself

Remove treatments or trials and refit the frequentist and Bayesian models in your browser, with the same methods as the published analysis.

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