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Biomedical subjects

Harry W Daniell

Publications and source records attributed to Harry W Daniell.

16 recordsLinked to original sources

Open-label pilot study of testosterone patch therapy in men with opioid-induced androgen deficiency.

UNLABELLED: We conducted a 24-week open-label pilot study of testosterone (T) patch therapy in 23 men with opioid-induced androgen deficiency (OPIAD). The T dosage was 5 mg/day for the first 12 weeks and 7.5 mg/day for the second 12 weeks. Seven subjects discontinued prematurely: 4 for noncompliance, 2 for skin irritation and 1 for hepatitis C treatment. In the "completers" population (n = 16), mean (SD) free T levels (normal range 52 to 280 pg/mL) were 28.5 (18.6) pg/mL at baseline, 72.8 (29.6) pg/mL on 5 mg/day (P < .001 vs. baseline), and 120.2 (69.5) pg/mL on 7.5 mg/day (P < .001 vs. baseline and P < .01 vs. 5 mg/day). Total T, dihydrotestosterone, and estradiol showed parallel changes. Sex hormone-binding globulin levels were elevated at baseline and decreased modestly with treatment (P < .05 vs. baseline at 5 mg/day; P < .01 vs. baseline at 7.5 mg/day). Luteinizing hormone levels were in the low-normal range at baseline and suppressed markedly with treatment (P < .001 vs. baseline at both doses). Androgen deficiency symptoms (ADSQ), sexual function (Watts SFQ), mood (PGWB), depression (BDI-II), and hematocrit levels showed improvement during treatment, generally more so at the 7.5 mg/day dosage (P < .001 vs. baseline for most parameters). Pain scores (BPI-SF) decreased slightly on 7.5 mg/day (interference score: P < .05 vs. baseline and 5 mg/day); the use of opioids did not change appreciably. The testosterone patches were generally well tolerated. PERSPECTIVE: Long-acting opioid preparations suppress the hypothalamic-pituitary-gonadal axis in men and produce a symptomatic state of opioid-induced androgen deficiency (OPIAD). Testosterone patch therapy at a dose of 7.5 mg/day normalizes hormone levels and appears to improve a number of quality of life parameters (eg, sexual function, well-being, mood) in men with OPIAD.

Administration, Cutaneous↗

DHEAS deficiency during consumption of sustained-action prescribed opioids: evidence for opioid-induced inhibition of adrenal androgen production.

UNLABELLED: Dehydroepandrosterone (DHEA)-dehydroepiandrosterone sulfate (DHEAS) deficiency often produces fatigue, depression, weakness, and sexual dysfunction, which improve during replacement therapy. DHEAS deficiency is a sensitive marker for generalized adrenal insufficiency, but it has not been related to opioid ingestion. DHEAS values were determined in 34 male and 32 female opioid-consuming outpatients aged 35-78 years, in stable health, and in 33 male and 53 female nonopioid-consuming control subjects. No subjects used anticonvulsants or corticosteriod medications, and none had malignant, collagen-vascular, or endocrine disease other than menopause or opioid-induced androgen deficiency. Adrenocorticotropic hormone (ACTH) values were measured in 94 of 152 subjects. DHEAS levels were lower in opioid consumers than in control subjects in a dose-related pattern (P < .01), were below age-specific norms in 67% of opioid consumers and 8% of controls (P < .001), and were below our laboratory's lowest detection limit (15 mug/dL) in 29% of opioid users and 1% of controls (P < .001). DHEAS values were also lower in opioid-consuming nonsmokers than in smokers (P < .05) and were unrelated to body mass index or concurrent hormonal replacement therapy. ACTH levels were normal and unrelated to opioid use. The combination of subnormal DHEAS levels in the presence of normal ACTH values in most opioid-consuming patients suggests that these low levels result from factors other than diminished adrenal ACTH stimulation. PERSPECTIVE: The study documents a dose-related DHEAS deficiency in a majority of nonhospitalized adults who are chronically consuming sustained-action oral or transdermal opioids for control of nonmalignant pain. This deficiency in these patients has not previously been recognized and is probably symptomatic. Evaluation of replacement therapy should receive high priority.

Adrenal Glands↗

Hypogonadism in men consuming sustained-action oral opioids.

Naturally occurring opiates (endorphins) diminish testosterone levels by inhibiting both hypothalamic gonadotrophin releasing hormone production and testicular testosterone synthesis. Heroin addicts treated with a single daily dose of methadone and nonaddicts receiving continuous intrathecal opioids quickly develop low luteinizing hormone and total testosterone levels. A similar pattern was sought in men consuming commonly prescribed oral opioids. Free testosterone (FT), total testosterone (TT), estradiol (E(2)), dihydrotestosterone (DHT), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured in 54 community-dwelling outpatient men consuming oral sustained-action dosage forms of opioids several times daily for control of nonmalignant pain. Hormone levels were related to the opioid consumed, dosage and dosage form, nonopioid medication use, and several personal characteristics and were compared with the hormone analyses of 27 similar men consuming no opioids. Hormone levels averaged much lower in opioid users than in control subjects in a dose-related pattern (P < .0001 for all comparisons). FT, TT, and E(2) levels were subnormal in 56%, 74%, and 74%, respectively, of opioid consumers. Forty-eight men (89%) exhibited subnormal levels of either FT or E(2). Either TT or E(2) level was subnormal in all 28 men consuming the equivalent of 100 mg of methadone daily and in 19 of 26 (73%) consuming smaller opioid doses. Eighty-seven percent (39 of 45) of opioid-ingesting men who reported normal erectile function before opioid use reported severe erectile dysfunction or diminished libido after beginning their opioid therapy. Commonly prescribed opioids in sustained-action dosage forms usually produce subnormal sex hormone levels, which may contribute to a diminished quality of life for many patients with painful chronic illness.

Journal Article↗

Narcotic-induced hypogonadism during therapy for heroin addiction.

Many patients receiving sustained-action narcotics during therapy for heroin addiction have symptoms of fatigue, depression, diminished libido, and impaired sexual function. They are rarely, however, evaluated for narcotic-induced hypogonadism, or treated with sex-hormone replacement. Studies are reviewed examining the influence of narcotic administration on sex-hormone levels. These document frequent, sometimes profound, deficiencies in many men and women treated with narcotics. We have documented improved quality of life during sex-hormone replacement therapy in patients with narcotic-induced hypogonadism, most of whom were receiving their narcotics for control of chronic pain. These studies suggest that similar hormone replacement therapy may assist patients receiving narcotics for treatment of heroin addiction.

Androgens↗