Ropinirole for the Treatment of Hyperprolactinemia: A Dose-Escalation Study of Efficacy and Tolerability.

CONTEXT: Treatment of hyperprolactinemia with ergoline dopamine agonists (DAs) can be complicated by intolerance and resistance. OBJECTIVE: This study examines the efficacy and tolerability of the nonergot DA ropinirole for the long-term treatment of hyperprolactinemia. METHODS: Twelve hyperprolactinemic women were treated with ropinirole in a 6-month, open-label, dose-escalation trial; 7 of the 12 continued treatment in an extension study for up to 17 months. Ropinirole doses were uptitrated to achieve normal prolactin (PRL) levels, restore menses, and eliminate galactorrhea. RESULTS: Two of the 12 participants were DA naive; 6 of 12 were ergot DA intolerant; and 1 of 12 had known ergot DA resistance. Baseline PRL levels were 126.2 ± 41.4 ng/mL (SEM). Ropinirole was uptitrated from 0.125 to 0.25 mg/h to a median total daily dose (TDD) of 2 mg/d (1-4 mg/d [interquartile range]). PRL normalization was achieved in 50% of the participants (5 with microadenomas and 1 with idiopathic hyperprolactinemia) at a median effective TDD of 1 mg/d. Of the patients achieving PRL normalization, 83% were ergot DA intolerant. A persistent partial biochemical response (PRL reduction >50% from baseline) was achieved in 17% of the participants. During treatment, menses resumed in 67% of amenorrheic patients; galactorrhea resolved in 67%. Mild adverse effects were reported in 92% of participants; however, ropinirole was not discontinued because of intolerance even among the 50% of individuals with a prior history of ergot DA intolerance and resultant medication discontinuation. CONCLUSION: These data demonstrate the efficacy and tolerability of ropinirole for the treatment of hyperprolactinemia in patients with microprolactinomas and idiopathic hyperprolactinemia and suggest ropinirole may represent a novel therapeutic alternative for treating hyperprolactinemic disorders in patients with ergot DA intolerance.

Defining Predictors of Weight Loss Response to Lorcaserin.

CONTEXT: Individual responses to weight loss (WL) medications vary widely and prediction of response remains elusive. OBJECTIVE: We investigated biomarkers associated with use of lorcaserin (LOR), a 5HT2cR agonist that targets proopiomelanocortin (POMC) neurons that regulate energy and glucose homeostasis, to identify predictors of clinical efficacy. METHODS: Thirty individuals with obesity were treated with 7 days of placebo and LOR in a randomized crossover study. Nineteen participants continued on LOR for 6 months. Cerebrospinal fluid (CSF) POMC peptide measurements were used to identify potential biomarkers that predict WL. Insulin, leptin, and food intake during a meal were also studied. RESULTS: LOR induced a significant decrease in CSF levels of the POMC prohormone and an increase in its processed peptide ß-endorphin after 7 days; ß-endorphin/POMC increased by 30% (P < .001). This was accompanied by a substantial decrease in insulin, glucose, and homeostasis model assessment of insulin resistance before WL. Changes in CSF POMC peptides persisted after WL (6.9%) at 6 months that were distinct from prior reports after diet alone. Changes in POMC, food intake, or other hormones did not predict WL. However, baseline CSF POMC correlated negatively with WL (P = .07) and a cutoff level of CSF POMC was identified that predicted more than 10% WL. CONCLUSION: Our results provide evidence that LOR affects the brain melanocortin system in humans and that effectiveness is increased in individuals with lower melanocortin activity. Furthermore, early changes in CSF POMC parallel WL-independent improvements in glycemic indexes. Thus, assessment of melanocortin activity could provide a way to personalize pharmacotherapy of obesity with 5HT2cR agonists.

Central Obesity Is Associated With an Increased Rate of Multisite Pain in Older Adults.

Objective: Central obesity has been associated with several adverse health events, but little research exists about the longitudinal effects of central obesity on multisite pain. The purpose of this study was to assess if central obesity, as measured by waist circumference measurement, was associated with an increased rate of having multisite pain among older adults aged 65 years and older. Design: The National Health and Aging Trends Study is a longitudinal cohort study initiated in 2011 and intended to be representative of Medicare beneficiaries in the contiguous United States. Methods: There were 7,145 community-dwelling participants included in this study. Data for this study were collected annually between 2011 and 2018. Researchers assessed if waist circumference risk level was associated with an increased rate ratio of multisite pain. Weighted data were used in a multivariable generalized estimating equation model that used a log link specified with a Poisson distribution. Results: Participants with high-risk waist circumferences (98 cm or greater for women and 109 cm or greater for men) had a 11% higher rate of multisite pain than those with low-risk waist circumferences [rate ratio (RR) 1.11, 95% CI: 1.07-1.15] adjusting for gender, age, race, education, probable major depression, arthritis, and multimorbidity count. Conclusion: As measured by waist circumference, central adiposity is associated with multisite pain in older adults. While more research is needed, reducing waist circumference may prove beneficial in reducing the burden of multisite pain.

Poor Lower Extremity Functioning Is Associated with Modest Increased Incidence of Probable Dementia.

Lower extremity functioning in older adults provides a measure of poor physical performance and can predict negative health outcomes. The consequences of reduced lower extremity functioning on cognitive decline, measured as time-varying variables, have not been well documented in previous studies. We aimed to evaluate whether lower extremity functioning is associated with an increased incidence rate of probable dementia among older adults using data from the National Health and Aging Trends Study (NHATS). Participants (n = 6457) were followed for 8 years to examine the relationship between lower extremity functioning, as measured by the Short Physical Performance Battery (SPPB), and incident probable dementia. Using weighted data, a multivariable Poisson regression with generalized estimating equations (GEE) was used to calculate incidence rate ratios (IRR), adjusting for covariates and clustering. Participants with low SPPB scores (0-5) had a 5% increase in incident probable dementia when compared with those who had good SPPB scores (10-12) in the adjusted model (IRR = 1.05; 95% CI = 1.04-1.07). Lower extremity functioning is associated with a modest increase in incident probable dementia. The SPPB score may be helpful in identifying subjects at risk of dementia. Efforts aimed at improving physical functioning may lead to better cognitive outcomes.