Studies with chronic Δ9- THC administration by 3 injections per week throughout several consecutive menstrual cycles strongly decreased serum levels of estradiol, progesterone and LH, and blocked ovulation and menses; nevertheless, animals developed tolerance to Δ9-THC,and these effects were overcame with timeAdditional experimental studies aimed at further characterizing the endocrine effects of Δ9-THC provided robust evidence that the hypothalamus, rather than the pituitary, is the specific target within the HPO axis responsible for dropping of serum gonadotropins levels upon treatment; indeed, Δ9-THC-induced decrease of gonadotropins levels was efficiently recovered by the administration of exogenous gonadotropin releasing hormone (GnRH),suggesting that the pituitary maintained responsiveness to hypothalamic hormones in the presence of Δ9-TH