7α-Methyl-19-Nortestosterone Maintains Sexual Behavior and Mood in Hypogonadal Men*

Abstract The synthetic steroid 7α-methyl-19-nortestosterone (MENT) is a potent androgen that is resistant to 5α-reductase. It thus has decreased activity at the prostate and may have advantages over testosterone-based regimens in long term treatment or as part of a male contraceptive. Administration to eugonadal men results in suppression of gonadotropins, but its ability to support androgen-dependent behavior has not been investigated. For sustained release administration, MENT acetate was used, because its diffusion characteristics were more suitable for use in implants. However, upon release the acetate is rapidly hydrolyzed, and MENT is the biologically active moiety in circulation. We studied the effects of MENT on sexual interest and activity, spontaneous erection, and mood states in comparison with testosterone enanthate (TE) in 20 Caucasian and Chinese hypogonadal men recruited in Edinburgh and Hong Kong (n = 10 in each center). Outcomes were measured using a combination of daily diaries, semistructured interviews, and questionnaires. Nocturnal penile tumescence (NPT) was also recorded in the Edinburgh group. After withdrawal of androgen replacement treatment (wash-out phase) for a minimum of 6 weeks, subjects were randomized to two groups in a cross-over design. Drug treatment regimens were of 6-week duration and consisted of two implants, each containing 115 mg MENT acetate, inserted sc into the upper arm and removed after 6 weeks and two injections of TE (200 mg, im) 3 weeks apart. MENT treatment resulted in stable plasma MENT concentrations of 1.4 ± 0.1 nmol/L after 3 weeks and 1.3 ± 0.1 nmol/L after 6 weeks (mean ± sem; all men). Nadir testosterone concentrations were 3.6 ± 0.6 nmol/L at the end of the wash-out phase and 9.4 ± 0.6 nmol/L 3 weeks after each injection. There were no differences in hormone concentrations between centers. There were no adverse toxicological effects. There were only minor differences between the two treatments. Both MENT and TE treatment resulted in significant increases in sexual interest and activity, spontaneous erection (both by self-report and NPT measurement), and increases in positive moods, with decreases in negative moods in the Edinburgh group. In the Hong Kong group, both treatments increased waking erection, with a trend toward increased sexual interest and activity. Mood states appeared to be less affected during the wash-out phase than in Edinburgh men and showed no significant response to either treatment. These results demonstrate that MENT has similar effects on sexual activity and mood states as testosterone in hypogonadal men. As NPT is a physiological androgen-dependant outcome, these data provide further evidence for the androgenicity of MENT. The lack of detected effect of either androgen in Hong Kong men other than on waking erection illustrates the importance of the cultural context of symptomatology and its measurement. The appropriate dose of MENT remains to be determined, but these results support its development as a potential androgen replacement therapy.

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Substance use, Unlike Dolutegravir, is Associated with Mood Symptoms in People Living with HIV

AIDS and Behavior ◽

10.1007/s10461-021-03272-2 ◽

2021 ◽

Author(s):

Lisa Van de Wijer ◽

Wouter van der Heijden ◽

Mike van Verseveld ◽

Mihai Netea ◽

Quirijn de Mast ◽

...

Keyword(s):

Substance Use ◽

Term Treatment ◽

Assessment Tools ◽

Self Report ◽

People Living With Hiv ◽

Antiretroviral Drug ◽

Long Term Treatment ◽

Living With Hiv ◽

Neuropsychiatric Side Effects

AbstractContradictory data have been reported concerning neuropsychiatric side effects of the first-line antiretroviral drug dolutegravir, which may be partly due to lack of control groups or psychiatric assessment tools. Using validated self-report questionnaires, we compared mood and anxiety (DASS-42), impulsivity (BIS-11), and substance use (MATE-Q) between dolutegravir-treated and dolutegravir-naive people living with HIV (PLHIV). We analyzed 194, mostly male, PLHIV on long-term treatment of whom 82/194 (42.3%) used dolutegravir for a median (IQR) of 280 (258) days. Overall, 51/194 (26.3%) participants reported DASS-42 scores above the normal cut-off, 27/194 (13.5%) were classified as highly impulsive, and 58/194 (29.9%) regularly used recreational drugs. Regular substance use was positively associated with depression (p = 0.012) and stress scores (p = 0.045). We observed no differences between dolutegravir-treated and dolutegravir-naive PLHIV. Our data show that depressed and anxious moods and impulsivity are common in PLHIV and associate with substance use and not with dolutegravir use.

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Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

Chinese Medicine ◽

10.1186/s13020-021-00456-9 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Ou Qiao ◽

Xinyu Zhang ◽

Yi Zhang ◽

Haixia Ji ◽

Zhi Li ◽

...

Keyword(s):

Synaptic Plasticity ◽

Complementary Medicine ◽

Term Treatment ◽

Biologically Active ◽

Combination Group ◽

Tnf Α ◽

Long Term Treatment ◽

Golgi Staining ◽

High Degree

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare Granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect against memory impairment in mice caused by d-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin–eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression (P < 0.05 or P < 0.001). Besides, the combination group markedly inhibited the levels of IL-1β, IL-6, and TNF-α in hippocampus (P < 0.001), as well as activities of SOD, CAT, and GSH-Px in serum (P < 0.001). By contrast, the combination group improved synaptic plasticity by enhancing SYN, PSD95, and GAP43 expression. Conclusions Taken together, these data supported the notion that CG combined with Mm might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic plasticity.

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Internet-Based Cognitive Therapy for Social Anxiety Disorder in Hong Kong: Therapist Training and Dissemination Case Series (Preprint)

10.2196/preprints.13446 ◽

2019 ◽

Author(s):

Graham R Thew ◽

Candice LYM Powell ◽

Amy PL Kwok ◽

Mandy H Lissillour Chan ◽

Jennifer Wild ◽

...

Keyword(s):

Hong Kong ◽

Anxiety Disorder ◽

Social Anxiety ◽

Cognitive Therapy ◽

Clinical Supervision ◽

Social Anxiety Disorder ◽

Cultural Context ◽

Case Series ◽

Therapist Training ◽

Self Report

BACKGROUND Guided internet-based psychological interventions show substantial promise for expanding access to evidence-based mental health care. However, this can only be achieved if results of tightly controlled studies from the treatment developers can also be achieved in other independent settings. This dissemination depends critically on developing efficient and effective ways to train professionals to deliver these interventions. Unfortunately, descriptions of therapist training and its evaluation are often limited or absent within dissemination studies. OBJECTIVE This study aimed to describe and evaluate a program of therapist training to deliver internet-based Cognitive Therapy for social anxiety disorder (iCT-SAD). As this treatment was developed in the United Kingdom and this study was conducted in Hong Kong with local therapists, an additional objective was to examine the feasibility, acceptability, and initial efficacy of iCT-SAD in this cultural context, based on data from a pilot case series. METHODS Training in iCT-SAD was provided to 3 therapists and included practice of the face-to-face format of therapy under clinical supervision, training workshops, and treating 6 patients with the iCT-SAD program. Training progress was evaluated using standardized and self-report measures and by reviewing patient outcomes. In addition, feedback from patients and therapists was sought regarding the feasibility and acceptability of the program. RESULTS The training program was effective at increasing therapists’ iCT-SAD knowledge and skills, resulting in levels of competence expected of a specialist Cognitive Behavioral Therapy practitioner. The 6 patients treated by the trainees all completed their treatment and achieved a mean pre- to posttreatment change of 53.8 points (SD 39.5) on the primary patient outcome measure, the Liebowitz Social Anxiety Scale. The within-group effect size (Cohen d) was 2.06 (95% CI 0.66-3.46). There was evidence to suggest that the patients’ clinical outcomes were sustained at 3-month follow-up. These clinical results are comparable to those achieved by UK patients treated by the developers of the internet program. Patient and therapist feedback did not identify any major cultural barriers to implementing iCT-SAD in Hong Kong; some modest language suggestions were made to assist understanding. CONCLUSIONS The therapist training implemented here facilitated the successful dissemination of an effective UK-developed internet intervention to Hong Kong. The treatment appeared feasible and acceptable in this setting and showed highly promising initial efficacy. A randomized controlled trial is now required to examine this more robustly. As therapist training is critical to the successful dissemination of internet interventions, further research to develop, describe, and evaluate therapist training procedures is recommended.

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Cerebralcare Granule® enhances memantine hydrochloride efficacy in APP/PS1 mice by ameliorating amyloid pathology and cognitive functions

10.21203/rs.3.rs-366097/v1 ◽

2021 ◽

Author(s):

Ou Qiao ◽

Xinyu Zhang ◽

Yi Zhang ◽

Haixia Ji ◽

Zhi Li ◽

...

Keyword(s):

Complementary Medicine ◽

Term Treatment ◽

Biologically Active ◽

Combination Group ◽

Tnf Α ◽

Long Term Treatment ◽

Golgi Staining ◽

High Degree

Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by memory deficits and cognitive decline. Current drugs can only relieve symptoms, but cannot really cure AD. Cerebralcare granule® (CG) is a Traditional Chinese medicine (TCM) containing a variety of biologically active compounds. In our previous studies, CG has shown a beneficial effect on memory impairment in mice caused by D-galactose. However, whether CG can be used as a complementary medicine for the treatment of AD remains unexplored. Here, we use a combination of CG and memantine hydrochloride (Mm) to treat Alzheimer-like pathology and investigate the effects and mechanisms in vivo. Methods The histology of brain was examined with Hematoxylin-eosin (HE) staining, Golgi staining and Thioflavin S staining. ELISA was applied to assess the expression levels or activities of CAT, SOD, GSH-Px, MDA, alanine aminotr-ansferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL) in serum, as well as the levels of IL-6, IL-1β, and TNF-α in the mice brain. Western blotting was used to assess the expression of β-secretase (BACE1), amyloid precursor protein (APP), APPβ, APPα, synaptophysin (SYN), growth-associated protein 43 (GAP43), and postsynaptic density 95 (PSD95). Results In the present study, the combination group (CG + Mm) significantly attenuated Alzheimer-like behavior without adverse effects in APP/PS1 mice, indicating its high degree of safety and efficacy after long-term treatment. CG + Mm reduced AD pathological biomarker Aβ plaque accumulation by inhibiting BACE1 and APP expression, while Mm has no similar effect. Besides, the combination group markedly inhibited the levels of IL-1β, IL-6, and TNF-α in the hippocampus, as well as activities of SOD, CAT, and GSH-Px in serum. By contrast, the combination group improved synaptic dysfunction by enhancing SYN, PSD95, and GAP43 expression. Conclusions Taken together, these data supported the notion that CG might ameliorate the cognitive impairment through multiple pathways, suggesting that CG could play a role as complementary medicine to increase anti-AD effect of chemical drugs by reducing Aβ deposition, neuroinflammation, oxidative damage, and improving synaptic.

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