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Broadly, across both preclinical and clinical studies, estradiol enhances while progesterone decreases nicotines reinforcing value (44)

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Strengths and Limitations The strengths of this meta-analysis include the large pooled sample size (24,000 participants, from multinational countries like USA, UK, South Korea, Canada, and Colombia), the integration of multiple biomarker types (nicotine metabolites, TSNAs, and cytokines), and the application of GRADE methodology to assess the certainty of evidence

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