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Opioid-induced Androgen Deficiency Discussion in Opioid Contracts

      To the Editor:
      The excellent article by Arnold et al
      • Arnold R.
      • Han P.
      • Seltzer D.
      Opioid contracts in chronic nonmalignant pain management: objectives and uncertainties.
      prompted us to suggest an addition to the text of most opioid contracts. It is our practice to improve the usefulness of these contracts to both patients and practitioners by including in them a discussion of opioid-induced androgen deficiency (OPIAD).
      Strong inhibition of androgen production quickly follows the onset of sustained-action opioid use, whether the opioids are administered orally,
      • Daniell H.
      Hypogonadism in men consuming sustained-action oral opioids.
      • Rajagopal A.
      • Vassilopoulou-Sellin R.
      • Palmer J.L.
      • et al.
      Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids.
      • Daniell H.
      • Lentz R.
      • Mazer N.
      Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.
      • Roberts L.J.
      • Finch P.M.
      • Pullan P.T.
      • et al.
      Sex hormone suppression by intrathecal opioids: a prospective study.
      transdermally,
      • Daniell H.
      • Lentz R.
      • Mazer N.
      Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.
      or intrathecally.
      • Rajagopal A.
      • Vassilopoulou-Sellin R.
      • Palmer J.L.
      • et al.
      Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids.
      • Roberts L.J.
      • Finch P.M.
      • Pullan P.T.
      • et al.
      Sex hormone suppression by intrathecal opioids: a prospective study.
      • Abs R.
      • Verhelst J.
      • Maeyaert J.
      • et al.
      Endocrine consequences of long-term intrathecal administration of opioids.
      • Paice J.
      • Penn R.
      • Ryan W.
      Altered sexual function and decreased testosterone in patients receiving intraspinal opioids.
      • Paice J.A.
      • Penn R.D.
      Amenorrhea associated with intraspinal morphine.
      These low androgen levels result in classic symptoms of hypogonadism in a majority of opioid-consuming men, with most of them exhibiting various combinations of fatigue, depression, hot flashes, night sweats, diminished libido, erectile dysfunction, and diminished sexual arousal and satisfaction. Low androgen levels also contribute to physical changes, including osteoporosis, anemia, and diminished muscle mass. Similar changes occur in opioid-consuming premenopausal women, most of whom demonstrate amenorrhea or anovulatory menstrual cycles soon after beginning sustained-action opioid use.
      • Abs R.
      • Verhelst J.
      • Maeyaert J.
      • et al.
      Endocrine consequences of long-term intrathecal administration of opioids.
      • Paice J.A.
      • Penn R.D.
      Amenorrhea associated with intraspinal morphine.
      • Schmittner J.
      • Schroeder J.R.
      • Epstein D.H.
      • Preston K.L.
      Menstrual cycle length during methadone maintenance.

      Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of non-malignant pain. J Pain. In press.

      Most premenopausal and postmenopausal women also demonstrate greatly diminished libido
      • Abs R.
      • Verhelst J.
      • Maeyaert J.
      • et al.
      Endocrine consequences of long-term intrathecal administration of opioids.
      • Paice J.A.
      • Penn R.D.
      Amenorrhea associated with intraspinal morphine.

      Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of non-malignant pain. J Pain. In press.

      at this time.
      Signs and symptoms of hypogonadism typically improve in men with OPIAD during replacement testosterone therapy
      • Daniell H.
      • Lentz R.
      • Mazer N.
      Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.
      and in the few women who have received hormone replacement therapy for opioid-related symptoms of hormone deficiency.
      • Abs R.
      • Verhelst J.
      • Maeyaert J.
      • et al.
      Endocrine consequences of long-term intrathecal administration of opioids.

      Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of non-malignant pain. J Pain. In press.

      In my private practice of general internal medicine, the discussion of OPIAD in our opioid contracts includes the potential usefulness of replacement hormonal therapy and potential complications of this therapy. We have found this information to be of help in establishing the patient-physician partnership described and recommended by Arnold et al,
      • Arnold R.
      • Han P.
      • Seltzer D.
      Opioid contracts in chronic nonmalignant pain management: objectives and uncertainties.
      which clearly is required for optimal chronic use of opioids. As part of this information exchange, we obtain sex-hormone levels in all outpatients about to begin chronic sustained-action opioid therapy and again with the development of symptoms of hypogonadism. Our contract includes discussion of testicular atrophy as a frequent complication of opioid therapy, which commonly progresses more rapidly during testosterone replacement therapy for OPIAD.
      • Daniell H.
      • Lentz R.
      • Mazer N.
      Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.
      Although this atrophy may become profound, patients are generally reassured to know that this complication is not accompanied by changes in penile size. It is our current practice to routinely document testicular size by using a Prader orchidometer before beginning chronic opioid therapy.

      References

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        • Han P.
        • Seltzer D.
        Opioid contracts in chronic nonmalignant pain management: objectives and uncertainties.
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        Hypogonadism in men consuming sustained-action oral opioids.
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        Sex hormone suppression by intrathecal opioids: a prospective study.
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        Endocrine consequences of long-term intrathecal administration of opioids.
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      1. Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of non-malignant pain. J Pain. In press.