The intermediate- and long-term effects of regular low-dose sustained-release (SR) morphine on the testosterone levels of people with persistent breathlessness are unknown.
Methods:
Exploratory analysis of a randomized controlled trial of the effects of regular SR morphine (0/8/16/24 mg every 24 hours) for persistent breathlessness associated with chronic obstructive pulmonary disease. Total testosterone was measured at baseline and at cessation (greater than or equal to three months on stable medication).
Results:
Among 20 participants (9 males; median treatment duration between measurements 169 days [IQR 162–175]), only 3 had substantial declines in testosterone levels during the study (morphine 8, 16, 24 mg groups). All three had worsening illness at the time of the second assessment. There was no apparent relationship between change in testosterone, morphine dose, and change in breathlessness.
Conclusions:
Substantial declines in testosterone were uncommon and were not apparently related to changes in morphine dose or breathlessness, but they were possibly related with worsening illness.
Get full access to this article
View all access options for this article.
References
1.
JohnsonMJ, YorkeJ, Hansen-FlaschenJ, et al.Towards an expert consensus to delineate a clinical syndrome of chronic breathlessness. Eur Respir J, 2017; 49(5):1602277.
2.
CurrowDC, SmithJ, DavidsonPM, et al.Do the trajectories of dyspnea differ in prevalence and intensity by diagnosis at the end of life? A consecutive cohort study. J Pain Symptom Manage, 2010; 39(4):680–690.
3.
CurrowDC, SmithJM, ChansriwongP, et al.Missed opportunity? Worsening breathlessness as a harbinger of death. A cohort study. Eur Respir J, 2018; 52(3):1800684.
4.
MiE, MiE, EwingG, et al.Associations between the psychological health of patients and carers in advanced COPD. Int J Chron Obstruct Pulmon Dis, 2017; 12:2813–2821.
5.
GyselsMC, BauseweinC, HigginsonIJ. Experiences of breathlessness: A systematic review of the qualitative literature. Palliat Support Care, 2007; 5(3):281–302.
6.
EkströmM, NilssonF, AbernethyAP, et al.Effects of opioids on breathlessness and exercise capacity in chronic obstructive pulmonary disease. A systematic review. Ann Am Thorac Soc, 2015; 12(7):1079–1092.
7.
JohnsonMJ, SbizzeraI, FairhurstC, et al.No excess harms from sustained-release morphine: A randomised placebo-controlled trial in chronic breathlessness. BMJ Support Palliat Care, 2020; 10(4):421–428.
8.
VerberktCA, van den Beuken-canEverdingen, ScholsJMGA, et al.Effect of sustained-release morphine for refractory breathlessness in chronic obstructive pulmonary disease on health status: A randomized clinical trial. JAMA Intern Med, 2020; 180(10):1306–1314.
RubinsteinA, CarpenterDM. Elucidating risk factors for androgen deficiency associated with daily opioid use. Am J Med, 2014; 127(12):1195–1201.
11.
RajagopalA, Vassilopoulou-SellinR, PalmerLJ, et al.Symptomatic hypogonadism in male survivors of cancer with chronic exposure to opioids. Cancer, 2004; 100(4):851–858.
12.
CurrowD, WattsGJ, JohnsonM, et al.A pragmatic, phase III, multisite, double-blind, placebo-controlled, parallel-arm, dose increment randomised trial of regular, low-dose extended-release morphine for chronic breathlessness: Breathlessness, Exertion And Morphine Sulfate (BEAMS) study protocol. BMJ Open, 2017; 7(7):e018100.
13.
BrambillaDJ, O”DonnellAM, MatsumotoAM, et al.Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf), 2007; 67(6):853–862.
14.
FerreiraD, KochovskaS, HonsonA, et al.Patients' and their caregivers' experiences with regular, low-dose, sustained-release morphine for chronic breathlessness associated with COPD: A qualitative study. BMJ Open Respir Res, 2022; 9(1):e001210; doi: 10.1136/bmjresp-2022-001210
15.
EkströmM, ElmbergV, LindowT, et al.Breathlessness measurement should be standardised for the level of exertion. Eur Respir J, 2018; 51(5):1800486.
16.
MuehlenbeinMP, HirschtickJL, BonerJZ, et al.Toward quantifying the usage costs of human immunity: Altered metabolic rates and hormone levels during acute immune activation in men. Am J Hum Biol, 2010; 22(4):546–556.
17.
PoetkerDM, RehDD. A comprehensive review of the adverse effects of systemic corticosteroids. Otolaryngol Clin North Am, 2010; 43(4):753–768.
18.
WangC, NieschlagE, SwerdloffR, et al.Investigation, treatment and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA and ASA recommendations. Eur J Endocrinol, 2008; 159(5):507–514.
19.
DavisonSL, BellR, DonathS, et al.Androgen levels in adult females: Changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab, 2005; 90(7):3847–3853.
20.
FeldmanHA, LongcopeC, DerbyCA, et al.Age trends in the level of serum testosterone and other hormones in middle-aged men: Longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab, 2002; 87(2):589–598.
21.
HarmanSM, MetterJE, TobinJD, et al.Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab, 2001; 86(2):724–731.
22.
ShiZ, AraujoAB, MartinS, et al.Longitudinal changes in testosterone over five years in community-dwelling men. J Clin Endocrinol Metab, 2013; 98(8):3289–3297.
23.
EkströmM, JohnsonMJ, TaylorB, et al.Breathlessness and sexual activity in older adults: The Australian Longitudinal Study of Ageing. NPJ Prim Care Respir Med, 2018; 28(1):20.
24.
BrambillaDJ, MatsumotoAM, AraujoAB, et al.The effect of diurnal variation on clinical measurement of serum testosterone and other sex hormone levels in men. J Clin Endocrinol Metab, 2009; 94(3):907–913.
