Arthritis & Rheumatism, 2013
Abstract
AbstractObjectiveTo determine whether low dosages (4.5 mg/day) of naltrexone reduce fibromyalgia severity as compared with the nonspecific effects of placebo. In this replication and extension study of a previous clinical trial, we tested the impact of low‐dose naltrexone on daily self‐reported pain. Secondary outcomes included general satisfaction with life, positive mood, sleep quality, and fatigue.
Methods
Thirty‐one women with fibromyalgia participated in the randomized, double‐blind, placebo‐controlled, counterbalanced, crossover study. During the active drug phase, participants received 4.5 mg of oral naltrexone daily. An intensive longitudinal design was used to measure daily levels of pain.
Results
When contrasting the condition end points, we observed a significantly greater reduction of baseline pain in those taking low‐dose naltrexone than in those taking placebo (28.8% reduction versus 18.0% reduction; P = 0.016). Low‐dose naltrexone was also associated with improved general satisfaction with life (P = 0.045) and with improved mood (P = 0.039), but not improved fatigue or sleep. Thirty‐two percent of participants met the criteria for response (defined as a significant reduction in pain plus a significant reduction in either fatigue or sleep problems) during low‐dose naltrexone therapy, as contrasted with an 11% response rate during placebo therapy (P = 0.05). Low‐dose naltrexone was rated equally tolerable as placebo, and no serious side effects were reported.
Conclusion
The preliminary evidence continues to show that low‐dose naltrexone has a specific and clinically beneficial impact on fibromyalgia pain. The medication is widely available, inexpensive, safe, and well‐tolerated. Parallel‐group randomized controlled trials are needed to fully determine the efficacy of the medication.
Topics
DOI 10.1002/art.37734 10.1002/art.37734 Younger et al. 2013, Younger 2013
Related articles
Add-Ons and Adjuncts · Adjunct Evidence Base
Effects of autologous platelet-rich plasma in recurrent implantation failure: a systematic review and meta-analysis
Pan Z et al., 2026 · Frontiers in endocrinology
[OBJECTIVE] The role of intrauterine PRP infusion in managing recurrent implantation failure (RIF) remains controversial despite its emerging clinical use. This systematic review aims to evaluate its therapeutic potential in RIF patients and further to investigate variations in outcomes based on transfer cycle type, embryo developmental stage, RIF diagnostic criteria, and endometrial thickness. [METHODS] We systematically searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science for randomized controlled trials (RCTs) investigating PRP treatment for RIF patients from the beginning of the database to May 2025. [RESULTS] This meta-analysis showed that PRP administration significantly improved clinical pregnancy rate (CPR) [OR = 3.18, 95%CI (2.45, 4.14), I2 = 3%], biochemical pregnancy rate (BPR) [OR = 2.84, 95%CI (2.22, 3.63), I2 = 0%], ongoing pregnancy rate (OPR) [OR = 3.41, 95%CI (2.08, 5.60), I2 = 30%] and live birth rate (LBR) [OR=5.10, 95%CI (1.95, 13.37), I2 = 75%] in women with RIF. However, PRP intrauterine infusion did not reduce miscarriage rate (MR). Notably, the preterm birth rate was significantly higher in the PRP group compared to controls [OR = 8.24, 95%CI (2.09, 32.41), I2 = 0%]. Subgroup analysis demonstrated that PRP improved CPR, BPR and LBR in both the fresh and frozen embryo transfer cycles. Additionally, while PRP increased CPR, LBR and reduced MR in blastocyst transfers [CPR OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%; LBR OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%; MR OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%], these effects were not observed in cleavage-stage embryo transfers. Moreover, PRP administration associated with a higher CPR [OR = 3.84, 95%CI (2.82, 5.23), I2 = 0%], OPR[OR = 4.13, 95%CI (1.79, 9.56), I2 = 48%], LBR [OR = 7.32, 95%CI (3.17, 16.90), I2 = 63%] and a lower MR [OR = 0.27, 95%CI (0.07, 0.96), I2 = 54%] in women with ≥3 prior implantation failure, it did not confer the same benefit to those with a history of ≥2 failed cycles. [CONCLUSION] These findings suggest a possible beneficial role for PRP on pregnancy outcomes to some extent in women with RIF, particularly in cases with ≥3 prior failed transfers, and blastocyst transfer may increase LBR and reduce miscarriage risk. However, further investigation is warranted to determine whether this treatment may pose an increased risk of preterm birth. [SYSTEMATIC REVIEW REGISTRATION] https://www.crd.york.ac.uk/prospero/, identifier CRD420251061511.
Bone Mineral Density · Peak Bone Mass
Impact of gender-affirming treatment on bone health in transgender and gender diverse youth
Ciancia S et al., 2022 · Endocrine connections
Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.
Male Factor Treatment · Medical Management
Antioxidants for male subfertility
de Ligny W et al., 2022 · Cochrane Database Syst Rev ·
The inability to have children affects 10% to 15% of couples worldwide. A male factor is estimated to account for up to half of the infertility cases with between 25% to 87% of male subfertility considered to be due to the effect of oxidative stress. Oral supplementation with antioxidants is thought to improve sperm quality by reducing oxidative damage. Antioxidants are widely available and inexpensive when compared to other fertility treatments, however most antioxidants are uncontrolled by regulation and the evidence for their effectiveness is uncertain. We compared the benefits and risks of different antioxidants used for male subfertility. To evaluate the effectiveness and safety of supplementary oral antioxidants in subfertile men. The Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED, and two trial registers were searched on 15 February 2021, together with reference checking and contact with experts in the field to identify additional trials. Selection Criteria: We included randomised controlled trials (RCTs) that compared any type, dose or combination of oral antioxidant supplement with placebo, no treatment, or treatment with another antioxidant, among subfertile men of a couple attending a reproductive clinic. We excluded studies comparing antioxidants with fertility drugs alone and studies that included men with idiopathic infertility and normal semen parameters or fertile men attending a fertility clinic because of female partner infertility. Data Collection and Analysis: We used standard methodological procedures recommended by Cochrane. The primary review outcome was live birth. Clinical pregnancy, adverse events and sperm parameters were secondary outcomes. MAIN We included 90 studies with a total population of 10,303 subfertile men, aged between 18 and 65 years, part of a couple who had been referred to a fertility clinic and some of whom were undergoing medically assisted reproduction (MAR). Investigators compared and combined 20 different oral antioxidants. The evidence was of 'low' to 'very low' certainty: the main limitation was that out of the 67 included studies in the meta-analysis only 20 studies reported clinical pregnancy, and of those 12 reported on live birth. The evidence is current up to February 2021. Live birth: antioxidants may lead to increased live birth rates (odds ratio (OR) 1.43, 95% confidence interval (CI) 1.07 to 1.91, P = 0.02, 12 RCTs, 1283 men, I(2) = 44%, very low-certainty evidence). Results in the studies contributing to the analysis of live birth rate suggest that if the baseline chance of live birth following placebo or no treatment is assumed to be 16%, the chance following the use of antioxidants is estimated to be between 17% and 27%. However, this result was based on only 246 live births from 1283 couples in 12 small or medium-sized studies. When studies at high risk of bias were removed from the analysis, there was no evidence of increased live birth (Peto OR 1.22, 95% CI 0.85 to 1.75, 827 men, 8 RCTs, P = 0.27, I(2) = 32%). Clinical pregnancy rate: antioxidants may lead to increased clinical pregnancy rates (OR 1.89, 95% CI 1.45 to 2.47, P < 0.00001, 20 RCTs, 1706 men, I(2) = 3%, low-certainty evidence) compared with placebo or no treatment. This suggests that, in the studies contributing to the analysis of clinical pregnancy, if the baseline chance of clinical pregnancy following placebo or no treatment is assumed to be 15%, the chance following the use of antioxidants is estimated to be between 20% and 30%. This result was based on 327 clinical pregnancies from 1706 couples in 20 small studies. Adverse events Miscarriage: only six studies reported on this outcome and the event rate was very low. No evidence of a difference in miscarriage rate was found between the antioxidant and placebo or no treatment group (OR 1.46, 95% CI 0.75 to 2.83, P = 0.27, 6 RCTs, 664 men, I(2) = 35%, very low-certainty evidence). The findings suggest that in a population of subfertile couples, with male factor infertility, with an expected miscarriage rate of 5%, the risk of miscarriage following the use of an antioxidant would be between 4% and 13%. Gastrointestinal: antioxidants may lead to an increase in mild gastrointestinal discomfort when compared with placebo or no treatment (OR 2.70, 95% CI 1.46 to 4.99, P = 0.002, 16 RCTs, 1355 men, I(2) = 40%, low-certainty evidence). This suggests that if the chance of gastrointestinal discomfort following placebo or no treatment is assumed to be 2%, the chance following the use of antioxidants is estimated to be between 2% and 7%. However, this result was based on a low event rate of 46 out of 1355 men in 16 small or medium-sized studies, and the certainty of the evidence was rated low and heterogeneity was high. We were unable to draw conclusions from the antioxidant versus antioxidant comparison as insufficient studies compared the same interventions. AUTHORS' In this review, there is very low-certainty evidence from 12 small or medium-sized randomised controlled trials suggesting that antioxidant supplementation in subfertile males may improve live birth rates for couples attending fertility clinics. Low-certainty evidence suggests that clinical pregnancy rates may increase. There is no evidence of increased risk of miscarriage, however antioxidants may give more mild gastrointestinal discomfort, based on very low-certainty evidence. Subfertile couples should be advised that overall, the current evidence is inconclusive based on serious risk of bias due to poor reporting of methods of randomisation, failure to report on the clinical outcomes live birth rate and clinical pregnancy, often unclear or even high attrition, and also imprecision due to often low event rates and small overall sample sizes. Further large well-designed randomised placebo-controlled trials studying infertile men and reporting on pregnancy and live births are still required to clarify the exact role of antioxidants.
Prescribing Safety · Off-Label Prescribing
Mortality risk reduction differs according to bisphosphonate class: a 15-year observational study
D Bliuc et al., 2019 · Osteoporos Int ·
In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.