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Unanticipated Opioid Tolerance in a Patient with Polycystic Ovary Syndrome
Session: EX-03
Thurs, April 19, 6:10-6:20 pm
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Unanticipated Opioid Tolerance in a Patient with Polycystic Ovary Syndrome

We present a challenging case of pain control for a female patient with polycystic ovary syndrome (PCOS) that underwent a total knee arthroplasty (TKA).  Our standard TKA protocol did not control her pain which led our patient to be on ketamine and high-dose opioids postoperatively.  Patients with PCOS have known dysregulation of the opioid and endocrine systems.   We hypothesize that our patient with PCOS had poor pain control due to dysregulation of her endogenous opioid system.

Materials and methods

Patient gave oral consent to submission of this case.

Results/Case report

Our patient is a 41-year-old female with a history of PCOS, hypothyroidism, and widespread osteoarthritis who underwent a TKA.  She had no history of home opioid use, but did report high opioid requirements after previous surgeries.  She received preoperative acetaminophen, prebabalin, and meloxicam in addition to an adductor canal block.  She had a spinal for her primary anesthetic which included intrathecal hydromorphone.  She was postoperatively prescribed oxycodone, acetaminophen, and meloxicam as well as IV opioids for breakthrough pain.

During her hospitalization, the patient's pain was markedly difficult to control.  She received increasing doses of oral medications—morphine sulfate, oxycodone, hydromorphone, and ketamine—as well as intravenous opioids.  She was discharged on POD #4 on dilaudid, acetaminophen, and ibuprofen.


This case presented challenges in pain control after TKA.  Our protocol is typically sufficient in patients without a history of opioid, steroid, or illicit drug use.  We feel that her polycystic ovary syndrome may have contributed to her history of post-operative opioid tolerance.

Polycystic ovary syndrome is a well-documented chronic disease that affects roughly 6 million women in the United States.  It is defined as a syndrome of ovulation dysfunction along with features of hyperandrogenism and polycystic ovaries.   The hallmark features of PCOS include obesity, infertility, insulin resistance and a dysregulated endogenous opioid system. 

We hypothesize that higher levels of endogenous opioid ligands played a role in our patient having significant opioid tolerance.    Multiple studies and reports have shown that chronic opioid therapy inhibits Gonadotropin-Releasing Hormone (GnRH) and results in lower testosterone levels in the body, which has been termed Opioid-Induced Androgen Deficiency (OPIAD).   Mechanisms that could account for our patient’s increased opioid tolerance in the setting of her PCOS include alterations of beta-endorphin synthesis, alterations of opioid receptor synthesis and expression, and alterations in binding characteristics of opioids.

While our literature review failed to find any studies linking opioid tolerance with PCOS, the relationship appears to be theoretically sound.  Previously described dysregulation of  the opioid and endocrine pathways in patients with PCOS may explain our patient’s significantly elevated opioid requirement in the absence of previous routine opioid use.


Al-Saqqa, Mariam.  “Polycystic Ovarian Syndrome (PCOS) Pathophysiology & Wider Health Issues. https://www.slideshare.net/peterbuck/polycystic-ovarian-syndrome-pcos-pa...

Demystifying Medicine.  “Polycystic Ovarian Syndrome Part II: Pathophysiology.” https://www.youtube.com/watch?v=BgNpATWfR5Y.

Eyvazzades, Aimee, et al. “The role of the endogenous opioid system in polycystic ovary syndrome.” Fertility and Sterility.  Volume 91, Issue 1, Pages 1-12.  July 2009.  http://www.fertstert.org/article/S0015-0282(09)01088-7/fulltext.

Smith, Howard and Elliott, Jennifer.  “Opioid-Induced Androgen Deficiency.”  Pain Physician. Volume 15 Issue 3S.  July 2012. http://www.painphysicianjournal.com/linkout?issn=1533-3159&vol=15&page=E...

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