For patients treated with TRT, total and free testosterone, complete blood count (CBC), prostate-specific antigen (PSA), estradiol, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and prolactin should be assessed at baseline. Endocrine Society guidelines recommend regular interval serum measurements of total testosterone, CBC, PSA, and estradiol between 3 and 6 months after treatment initiation, then every 3 to 12 months. To assess treatment response, the authors recommend frequent and serial use of the ADAM questionnaire and the Sexual Health Inventory for Men.

For men with concerns about fertility, testosterone enhancement with clomiphene citrate, a selective estrogen receptor modulator, may be considered. US Food and Drug Administration approved for the treatment of ovulatory dysfunction in females who wish to become pregnant, clomiphene citrate is also incorporated into urologic clinical practice at low dosages for the treatment of infertility and hypogonadism in men.

The agent inhibits central estrogen feedback and upregulates endogenous hypothalamic function. This leads to increased LH, FSH, and endogenous testosterone levels and enhanced spermatogenesis while avoiding negative effects on the HPG axis that characterizes exogenous testosterone therapy.

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“Given suppression of the HPG axis in OPIAD, clomiphene citrate is a logical treatment consideration,” the authors reported. The senior study author reports “excellent responses” in clinical practice “without adverse effects” when used in men with OPIAD, including improved quality of life and semen analysis. Men should be monitored similarly to those who receive exogenous TRT.

The authors called for larger prospective randomized trials to assist in developing consensus criteria for the diagnosis and management of patients with OPIAD. Validated questionnaires “to address baseline and postintervention outcomes related to quality of life, sexual desire, erectile function, libido, fertility, and pain perception” should be implemented in such studies.


1. O’Rourke TK Jr, Wosnitzer MS. Opioid-induced androgen deficiency (OPIAD): Diagnosis, management, and literature review. Curr Urol Rep. 2016:17:76.