In female rats, daily caffeine (10‑40 mg/kg) for three weeks lowered kidney and liver weight, reduced white blood cells, dropped gonadotropin‑releasing hormone (GnRH) and progesterone, raised inflammation marker TNF‑α, and messed up the estrous cycle, but it didn’t change blood lipids. All of these changes went back to normal after a three‑week caffeine break.

The consumption of caffeinated beverages has become deeply ingrained in modern society, with coffee, tea, and energy drinks being among the most commonly consumed sources of caffeine. Its physiological effects on the cardio-metabolic system have been reported in males. Hematological parameters and lipid profiling are crucial in the diagnosis of cardio-metabolic disorders. Given the growing prevalence of cardiovascular diseases among women and the potential role of caffeine consumption in modulating lipid profiles and hematopoiesis, a comprehensive investigation into this relationship was warranted using a female animal model. The phase of recovery from its effects was also considered in this study. Thirty-five adult female Wistar rats were randomly divided into seven groups (n = 5). Group I was the control and received distilled water (0.2 mL/Kg/day). Groups II-IV received daily oral doses of caffeine (10, 20, and 40 mg/Kg/day, respectively) for 21 days. Groups V-VII received similar caffeine doses for 21 days, followed by a 21-day withdrawal (recovery) period. The estrous cycle was assessed by unstained and staining techniques, full blood indices was determined by a hematology analyzer. Serum Tumor necrotic factor-alpha (TNF-α), lipid and hormonal profiles were assayed by ELISA techniques. Statistical analysis employed one way ANOVA with significance taken at p < 0.05. The findings of this study showed that caffeine reduced the kidney and liver weights, reduced white blood cell count, Gonadotropin releasing hormone level and further irreversibly reduced progesterone levels, but maintained the lipid profile level. Caffeine increased the level of TNF-α, but adversely impacted the phases of the estrous cycle by reducing their occurrences. These alterations were however reversed during withdrawal from caffeine. Hence, this study highlights that though caffeine may impact immune function, cardiovascular, reproductive and metabolic health, the withdrawal or stoppage of its intake can result in restoration of the altered changes in the body overtime.