Hypogonadotropic Hypogonadism Caused by Opioid Treatment for Nonmalignant Chronic Pain!!
A 42-year-old male patient suffered from severe pain after left brachial plexus injury by traffic accident. Because his pain was severe and uncontrolled by regular analgesics such as nonsteroidal anti-inflammatory drugs, anticonvulsants, and buprenorphine, transdermal fentanyl was administered in hospital. About 4 months after the treatment with transdermal fentanyl (4.2 mg/day), he felt a general fatigue, loss of libido, and erectile dysfunction for the first time. He had no appreciable past history except for traffic injury. He had also received diclofenac sodium, gabapentin, pregabalin and clonazepam. A physical examination demonstrated no significant findings including loss of hircus and pubic hair. Radiography of the thorax, as well as an electrocardiogram, was normal. The results of routine laboratory and urine findings were within normal ranges except for slight anemia. Morning (AM 8:00) endocrine examinations including serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxin (FT4), insulin-like growth factor-1 (IGF-1), prolactin (PRL), adrenocorticotropin (ACTH), cortisol, dehydroepiandrosterone-sulfate (DHEA-S), and urinary cortisol were within normal ranges. On the other hand, serum luteinizing hormone (LH) and follicle stimulating hormone (FSH), total testosterone, and free testosterone were decreased. Hormone stimulating tests including thyrotropin-releasing hormone (TRH, 0.5 mg), corticotropin-releasing hormone (CRH, 0.1 mg), and growth hormone-releasing peptide 2 (GHRP-2, 0.1 mg) showed normal reactions of TSH, ACTH, cortisol, and growth hormone (GH), respectively. On the other hand, in LH-releasing hormone (LH-RH, 0.1 mg) stimulating test, FSH reaction was delayed (Table 2). These findings showed that he had hypogonadotropic hypogonadism. How to cure this condition?
@shamita Several mechanisms are suggested to explain opioid-induced hypogonadism. Both endogenous and exogenous opioids, can bind opioid receptors primarily in the hypothalamus. Opioids have been shown to decrease the release of gonadotropin-releasing hormone (GnRH) and disrupt its normal pulsatility in the hypothalamus, resulting in a reduction of the release of LH and FSH from the pituitary gland and that of testosterone and estradiol from the gonads. Direct effects of opioids on the pituitary gland and gonads have also been suggested. Therefore, patients with opioid-induced hypogonadism have low serum testosterone/estradiol with normal or low serum LH/FSH levels as shown in the present case. Some studies evaluating the effect of opioid on the endocrine system in humans have shown that they have high serum prolactin levels leading to inhibit the secretion of GnRH [9, 33, 34]. However, most of the opioid treatment has no effect on serum prolactin levels as shown in the present case. Furthermore, opioids have also been shown to decrease adrenal androgen, an important precursor of both testosterone in men and estradiol in women. However, the present case has no decreased adrenal androgen such as DHEA-S.