The Effects of Estrogen and Progestin on Endogenous Opioid Activity in Oophorectomized Women*

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Abstract
Sex steroids may modulate the secretion of β-endorphin (β-EP). Naloxone (Nal), an opioid antagonist, hasbeen used as a probe of central opioid activity. Nal-evokedresponses of PRL and LH were evaluated in the midluteal (ML)and late follicular (LF) phases of ovulatory women (Pre) andcompared to responses of oophorectomized women before andafter the administration of conjugated estrogens (CE) and againafter CE and progestin administration. In the ML and LFphases, serum LH increased significantly (P <0.05 and P <0.01, respectively) during Nal infusion for 4 h, while PRL didnot change. In oophorectomized women, there were no significantchanges in LH or PRL during Nal infusion. After 3 weeksof CE treatment (1.25 mg daily), LH increased during Nalinfusion (P < 0.05), as did PRL (P < 0.01). After treatment withCE and medroxyprogesterone acetate (MPA), LH and PRL bothincreased (P < 0.05 and P < 0.01, respectively). The area underthe LH curve during Nal infusion after CE and MPA treatmentwas greater than that after CE alone. Both of these responseswere comparable to those of the LF and ML phases of Prewomen. During Nal infusion, LH pulse frequency increased inthe ML compared to the LF phase of the cycle and, in oophorectomizedwomen, was greater after CE and CE with MPAtreatment compared to pretreatment values (P < 0.05). LHamplitudes during Nal infusion were highest in the ML phaseand after CE and MPA treatment in oophorectomized women,and these LH amplitudes were similar. No correlation was foundbetween peripheral plasma β-EP and Nal-evoked LH responses.No differences were evident in plasma β-EP levels between Preand oophorectomized women. In conclusion, 1) endogenousopioid activity is low in oophorectomized women; 2) treatmentwith estrogen increases opioid activity, and the addition of aprogestin increases this activity further; and 3) these data supportthe contention that sex steroids exert a profound influenceon endogenous opioid activity.