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Biology of Sex Differences Jan 2024Androgens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido....
BACKGROUND
Androgens are important sex hormones in both men and women and are supplemented when endogenous levels are low, for gender transitioning, or to increase libido. Androgens also circulate at higher levels in women with polycystic ovarian syndrome, a condition that increases the risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via downregulation of GPER.
METHODS
The impact of the non-aromatizable androgen dihydrotestosterone (DHT), the glucocorticoid dexamethasone, and the progestin medroxyprogesterone acetate (all 100 nM for 24 h) on GPER and ERα expression was assessed in cultured vascular smooth muscle cells using droplet digital PCR (ddPCR). To assess the in vivo impact of the DHT-induced downregulation of GPER, female ovary-intact C57Bl/6 mice at 15-16 weeks of age were treated with silastic capsules containing DHT for 4 weeks, one with a dosage expected to mimic human male DHT levels and another to double the expected human concentration (n = 8-9/group).
RESULTS
In cultured vascular smooth muscle cells, GPER mRNA was decreased by DHT (P = 0.001) but was not impacted by dexamethasone or medroxyprogesterone. In contrast, ERα expression in cultured cells was significantly suppressed by all three hormones (P < 0.0001). In control mice or mice treated with a single or double dose of DHT, a dose-dependent increase in body weight was observed (control 22 ± 2 g, single dose 24 ± 2 g, double dose 26 ± 2 g; P = 0.0002). Intracarotid stiffness measured via pulse wave velocity showed a more than two-fold increase in both DHT-treated groups (control 1.9 ± 0.3 m/s, single dose 4.3 ± 0.8 m/s, double dose 4.8 ± 1.0 m/s). This increase in arterial stiffness occurred independent of changes in blood pressure (P = 0.59). Histological analysis of aortic sections using Masson's trichrome showed a significant decrease in collagen between the control group (24 ± 5%) and the double dose group (17 ± 3%, P = 0.007), despite no changes in aortic wall thickness or smooth muscle content. Lastly, ddPCR showed that in vivo DHT treatment decreased aortic expression of both GPER (control 20 ± 5, single dose 10.5 ± 5.6, double dose 10 ± 4 copies/ng; P = 0.001) and ERα (control 54 ± 2, single dose 24 ± 13, and double dose 23 ± 12 copies/ng; P = 0.003).
CONCLUSIONS
These findings indicate that androgen promotes arterial stiffening and cardiovascular damage in female mice and is associated with decreased estrogen receptor expression. These data are important for transgender men, women using testosterone for fitness or reduced libido, as well as patients with polycystic ovarian syndrome.
Topics: Female; Humans; Male; Animals; Mice; Infant, Newborn; Dihydrotestosterone; Androgens; Estrogen Receptor alpha; Polycystic Ovary Syndrome; Pulse Wave Analysis; Estrogens; Receptors, Estrogen; Dexamethasone
PubMed: 38263051
DOI: 10.1186/s13293-024-00586-3 -
Journal of Clinical Medicine Jan 2024Treatment-emergent sexual dysfunction (TESD) is one of the most frequent and persistent adverse effects of antidepressant medication. Sexual dysfunction (SD) secondary...
UNLABELLED
Treatment-emergent sexual dysfunction (TESD) is one of the most frequent and persistent adverse effects of antidepressant medication. Sexual dysfunction (SD) secondary to SSRIs occurs in >60% of sexually active patients and >80% of healthy volunteers, with this causing treatment discontinuation in >35% of patients. However, this factor is rarely addressed in routine examinations, and only 15-30% of these events are spontaneously reported. A strategy of switching to a different non-serotonergic antidepressant could involve a risk of relapse or clinical worsening due to a lack of serotonergic activity. Vortioxetine appears to have less impact on sexual function due to its multimodal mechanism of action. No studies have been published on the effectiveness of switching to vortioxetine in patients with poorly tolerated long-term antidepressant-related SD in naturalistic settings.
STUDY OBJECTIVES
To determine the effectiveness of switching to vortioxetine due to SD in a routine clinical practice setting.
METHODOLOGY
observational pragmatic and naturalistic study to determine the effectiveness of the switch to vortioxetine (mean dosage 13.11 ± 4.03) in 74 patients aged 43.1 ± 12.65 (54% males) at risk of discontinuing treatment due to sexual dysfunction. The PRSexDQ*- SALSEX scale ( Psychotropic-Related Sexual Dysfunction Questionnaire) was applied at two moments: baseline visit and after 3 months of follow-up.
RESULTS
global Sexual Dysfunction (SD) measured with the SALSEX scale decreased significantly between the baseline visit (10.32; SD 2.73) and the follow-up visit (3.78; SD 3.68), < 0.001. There was a significant improvement ( < 0.001) at the endpoint including decreased libido, delay of orgasm, anorgasmia and arousal difficulties in both sexes. After switching to vortioxetine, 83.81% of patients experienced an improvement in sexual function (43.2% felt greatly improved). Most patients (83.3%) who switched to vortioxetine continued treatment after the follow-up visit. A total of 58.1% of patients showed an improvement in depressive symptoms from the baseline visit.
CONCLUSION
switching to vortioxetine is an effective and reliable strategy to treat patients with poorly tolerated previous antidepressant-related sexual dysfunction in real-life clinical settings.
PubMed: 38256680
DOI: 10.3390/jcm13020546 -
Sexual Medicine Dec 2023Anorgasmia is a poorly understood phenomenon defined as either a lifelong or acquired consistent inability to achieve ejaculation. Despite the prevalence of anorgasmia,...
INTRODUCTION
Anorgasmia is a poorly understood phenomenon defined as either a lifelong or acquired consistent inability to achieve ejaculation. Despite the prevalence of anorgasmia, there is currently no established treatment for the condition.
AIMS
To report a unique case of a patient with lifelong anorgasmia who was able to achieve his first orgasm with off-label use of flibanserin.
METHODS
The present case study relies on the patient's self-report and a review of the relevant literature. The patient provided written informed consent.
RESULTS
A 28-year-old male presented to our office with complaints of lifelong anorgasmia, without any signs of erectile dysfunction. He reported good libido and energy levels and denied any urinary symptoms or history of depression. The patient failed medical management with numerous off-label medications, including bupropion and bremelanotide. Despite having received 4 or 5 sex therapy sessions over 3 months, the patient reported that this treatment approach was not effective. Off-label use of flibanserin was then initiated, and after 28 to 32 doses over 4 weeks, he achieved his first orgasm. Notably, the patient experienced nocturia and insomnia. The follow-up International Index of Erectile Function score marginally improved by 2 points without any improvement in the overall satisfaction subdomain.
CONCLUSION
This case highlights the challenges of managing anorgasmia and anejaculation in a young male patient. A stepwise approach involving pharmacotherapy and sex therapy was not successful. However, the off-label use of flibanserin ultimately resulted in the patient achieving his first orgasm, albeit with some side effects. Further studies are needed to evaluate the efficacy and safety of flibanserin in men for this indication.
PubMed: 38222292
DOI: 10.1093/sexmed/qfad066 -
Archives of Sexual Behavior Mar 2024Over the past 30 years, an increasing number of people have identified within the asexual (ACE) spectrum recognizing an absence/low/situational sexual attraction to...
Over the past 30 years, an increasing number of people have identified within the asexual (ACE) spectrum recognizing an absence/low/situational sexual attraction to individuals of any gender. The current study aims to deepen the knowledge of sexual desire, erotic fantasies, and related emotions within the ACE spectrum. A total of 1072 Italian volunteers were recruited to take part to the present study via social media. Data were collected from October 2021 to January 2022 using the Sexual Desire and Erotic Fantasies questionnaire and the Sexual Desire Inventory-2. Participants were divided into four groups: asexual, demisexual, gray-asexual, and questioning. Focusing on sexual desire, asexual people reported significantly lower scores than the other groups in all the dimensions except for "negative feelings to sexual desire," while demisexual participants showed the higher scores in all the domains except for "negative feelings to sexual desire." The questioning group reported the highest scores in the "negative feelings toward sexual desire" compared to the asexual and demisexual ones. The asexual group reported significantly lower scores than the other groups in fantasies frequency, fantasies importance, negative emotions, and sharing and experiencing. The demisexual group showed higher frequency of romantic fantasies than the asexual and gray-asexual ones. The results showed some specific patterns of desire and fantasies among the asexual, gray-asexual, demisexual, and questioning groups. These data may provide relevant material to clinicians working with asexual patients who need greater awareness about the diversity and heterogeneity of the sexual experience within the ACE spectrum.
Topics: Humans; Fantasy; Sexual Behavior; Libido; Gender Identity; Emotions
PubMed: 38212438
DOI: 10.1007/s10508-023-02784-3 -
Nutrients Dec 2023, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the... (Review)
Review
, also known as "zombie fungus", is a non-poisonous mushroom that parasitizes insects for growth and development by manipulating the host system in a way that makes the victim behave like a "zombie". These species produce promising bioactive metabolites, like adenosine, β-glucans, cordycepin, and ergosterol. has been used in traditional medicine due to its immense health benefits, as it boosts stamina, appetite, immunity, longevity, libido, memory, and sleep. Neuronal loss is the typical feature of neurodegenerative diseases (NDs) (Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS)) and neurotrauma. Both these conditions share common pathophysiological features, like oxidative stress, neuroinflammation, and glutamatergic excitotoxicity. bioactives (adenosine, N-(2-hydroxyethyl)-adenosine, ergosta-7, 9 (11), 22-trien-3β-ol, active peptides, and polysaccharides) exert potential antioxidant, anti-inflammatory, and anti-apoptotic activities and display beneficial effects in the management and/or treatment of neurodegenerative disorders in vitro and in vivo. Although a considerable list of compounds is available from , only a few have been evaluated for their neuroprotective potential and still lack information for clinical trials. In this review, the neuroprotective mechanisms and safety profile of extracts/bioactives have been discussed, which might be helpful in the identification of novel potential therapeutic entities in the future.
Topics: Neuroprotective Agents; Cordyceps; Agaricales; Neuroprotection; Adenosine
PubMed: 38201932
DOI: 10.3390/nu16010102 -
Journal of Family Medicine and Primary... Nov 2023Although studies have shown that bariatric surgery can have a positive effect on the patient's sexual function, there are still disagreements and contradictions in this...
INTRODUCTION
Although studies have shown that bariatric surgery can have a positive effect on the patient's sexual function, there are still disagreements and contradictions in this regard. The present study is aimed to evaluate semen parameters, hormonal changes of FSH, LH, testosterone, and libido following bariatric surgery.
METHODS
The present research as a prospective study was performed on 20 male candidates for bariatric surgery referred to Golestan and Aria hospitals in Ahvaz in 2021. Semen parameters (volume, count, motility, and the percentage of sperm with normal morphology), hormonal profile (including FSH, LH test hormones), and sexual function were evaluated using the International Index of Erectile Function (IIEF-5) questionnaire before and 6 months after the surgery.
RESULTS
The results of this study indicated that semen parameters did not change significantly 6 months after surgery in comparison with before the surgery ( < 0.05). After the operation, just the total level of testosterone increased significantly (2.23 nmol/L vs. 2.74, = 0.009). However, LH and FSH levels did not change significantly six months after surgery ( = 0.858 and = 0.287). The results indicated significant improvement in IIEF score after the operation ( = 0.011).
CONCLUSION
The findings of the present study indicated that the decrement of weight as a result of bariatric surgery had a favorable effect on the levels of serum testosterone and sexual performance, while semen parameters did not improve after surgery.
PubMed: 38186840
DOI: 10.4103/jfmpc.jfmpc_413_23 -
Pharmacology 2024Hypoactive sexual desire disorder (HSDD) in premenopausal women involves biological, psychological, and social aspects. In the European Society for Sexual Medicine... (Review)
Review
BACKGROUND
Hypoactive sexual desire disorder (HSDD) in premenopausal women involves biological, psychological, and social aspects. In the European Society for Sexual Medicine meeting in Rotterdam in February 2023, several leading experts in the field discussed the multifaceted nature of this disorder and the state of the art regarding treatment at a round table. This review reflects the information discussed at this event and further discusses current controversies.
SUMMARY
HSDD is the most prevalent female-estimated sexual disorder reported by 28% of the 40% premenopausal women with sexual dysfunction. Flibanserin and bremelanotide are the only approved medications to treat HSDD in the USA, and none are approved in Europe. Lybrido, Lybridos, and Lorexys are under development. There are several psychological factors with impact in sexual desire, including depression and sexual abuse. Feminine sexual scripts, the pleasure gap, and structural inequalities also affect sexual desire. Evidence strongly supports the value of combining medical and psychological approaches in the treatment of HSDD, but there is ongoing controversy regarding the pharmacological treatment of young women with HSDD. However, some women seem open and would like to have access to drug treatment.
KEY MESSAGES
The treatment of HSDD in young women requires a mixed treatment approach that addresses the disorder's complexity. Despite clinicians seeming to be divided between using pharmacological and/or psychosocial approaches, some women might respond better to one type of intervention over the others. This calls for the development of tools that assess the best approach for each person, including their will and informed choice.
Topics: Female; Humans; Sexual Dysfunctions, Psychological; Sexual Behavior; Libido; Premenopause; Europe
PubMed: 38151009
DOI: 10.1159/000535587 -
Animal : An International Journal of... Jan 2024Seasonality of reproductive activity in rams and bucks is the major constraint in temperate and subtropical zones. Rapid alternation between 1 month of short days and 1...
Seasonality of reproductive activity in rams and bucks is the major constraint in temperate and subtropical zones. Rapid alternation between 1 month of short days and 1 month of long days (LD) over three years in lightproof buildings eliminates this seasonality. We examined if this would also work in open barns, using only supplementary light. Over two years, one group of bucks (n = 7) was subjected to alternate 1 month of LD and 1 month of permanent light (LD-LL) and another group (n = 7) to alternate 1 month of LD and 1 month of natural light (LD-NL). A simultaneous control group, used for both experiments (CG1, n = 6; CG2, n = 6), remained under natural photoperiod. BW, testis weight (TW), plasma testosterone (T) and cortisol (C) were evaluated in all bucks. CG1 and CG2 bucks showed identical dramatic seasonal variations in BW (stable or decreasing in summer), TW (from 85 ± 12 g in February to 127 ± 7 g in July) and T (from 2.7 ± 1.2 ng/mL in January-April to 24.3 ± 3.2 ng/mL in June-October). By contrast, BW of LD-LL and LD-NL bucks increased regularly during the experiment. From 5 and 9 months after the experiment onset, LD-LL and LD-NL bucks, respectively, maintained constant TW of 115 ± 5 g until the experiment end. After the first 3 months <5 ng/mL, T of LD-LL bucks remained constant (5-10 ng/mL) until the experiment end. By contrast, T of LD-NL bucks showed four periods of low (<5 ng/mL) and two periods of high concentrations (18.1 ± 2.6 and 11.9 ± 3.4 ng/mL). Plasma C remained low (5-8 ng/mL) and did not change with group or light treatment. These results show for the first time in any seasonal photoperiodic species that it is possible to maintain the sexual activity of males all year round in open buildings using alternating periods of LD and LL. By contrast, return to NL instead of LL every other month does not prevent seasonality in T concentration. These results raise interesting questions about the photoperiodic control of neuroendocrine regulation of seasonal sexual activity and suggest that these treatments can be used to manage males in open barns in farms and in artificial insemination centres. (Spanish and French versions of the full text are available as Supplementary Materials S1 and S2).
Topics: Animals; Sheep; Male; Photoperiod; Seasons; Circadian Rhythm; Testis; Testosterone; Sheep, Domestic; Goats
PubMed: 38103431
DOI: 10.1016/j.animal.2023.101041 -
Frontiers in Genome Editing 2023is expressed in migrating primordial germ cells (PGCs) to protect them from apoptosis, and it is known to be a critical factor for germline development of both sexes in...
is expressed in migrating primordial germ cells (PGCs) to protect them from apoptosis, and it is known to be a critical factor for germline development of both sexes in several organisms. However, to date, live knockout (KO) cattle have not been reported, and the specific role of in male cattle, or bulls, remains unexplored. This study generated KO cattle cytoplasmic microinjection of the CRISPR/Cas9 system produced bovine zygotes and evaluated the effect of elimination on bovine germline development, from fetal development through reproductive age. The co-injection of two selected guide RNA (gRNA)/Cas9 ribonucleoprotein complexes (i.e., dual gRNA approach) at 6 h post fertilization achieved a high KO rate in developing embryos. Subsequent embryo transfers resulted in a 31% ( = 8/26) pregnancy rate. A 75% ( = 6/8) total KO rate (i.e., 100% of alleles present contained complete loss-of-function mutations) was achieved with the dual gRNA editing approach. In KO fetal testes, PGCs were found to be completely eliminated by 41-day of fetal age. Importantly, despite the absence of germ cells, seminiferous tubule development was not impaired in KO bovine testes during fetal, perinatal, and adult stages. Moreover, a live, KO, germline-ablated bull was produced and at sexual maturity he exhibited normal libido, an anatomically normal reproductive tract, and intact somatic gonadal development and structure. Additionally, a live, KO, germline-ablated heifer was produced. However, it was evident that the absence of germ cells in KO cattle compromised the normalcy of ovarian development to a greater extent than it did testes development. The meat composition of KO cattle was unremarkable. Overall, this study demonstrated that the absence of in cattle leads to the specific deficiency of both male and female germ cells, suggesting the potential of KO cattle to act as hosts for donor-derived exogenous germ cell production in both sexes. These findings contribute to the understanding of function in cattle and have valuable implications for the development of novel breeding technologies using germline complementation in KO germline-ablated hosts.
PubMed: 38089499
DOI: 10.3389/fgeed.2023.1321243 -
PloS One 2023In Uganda, approximately 170,000 confirmed COVID-19 cases and 3,630 deaths have been reported as of January 2023. At the start of the second COVID-19 wave, the Ugandan...
BACKGROUND
In Uganda, approximately 170,000 confirmed COVID-19 cases and 3,630 deaths have been reported as of January 2023. At the start of the second COVID-19 wave, the Ugandan health system was overwhelmed with a sudden increase in the number of COVID-19 patients who needed care, and the Ministry of Health resorted to home-based isolation and care for patients with mild to moderate disease. Before its rollout, the COVID-19 home-based care strategy had neither been piloted nor tested in Uganda.
OBJECTIVE
To explore the experiences of COVID-19 patients managed at home in Uganda.
METHODS
This was a qualitative study that was conducted to explore the lived experiences of COVID-19 patients managed at home. The study was carried out among patients who presented to three hospitals that were designated for treating COVID-19 patients in Uganda. COVID-19 patients diagnosed at these hospitals and managed at home were followed up and contacted for in-depth telephone interviews. The data were analysed using thematic content analysis with the aid of NVIVO 12.0.0 (QRS International, Cambridge, MA).
RESULTS
Participants experienced feelings of fear and anxiety: fear of death, fear of losing jobs, fear of infecting loved ones and fear of adverse events such as loss of libido. Participants also reported feelings of loneliness, hopelessness and depression on top of the debilitating and sometimes worsening symptoms. In addition to conventional medicines, participants took various kinds of home remedies and herbal concoctions to alleviate their symptoms. Furthermore, COVID-19 care resulted in a high economic burden, which persisted after the COVID-19 illness. Stigma was a major theme reported by participants. Participants recommended that COVID-19 care should include counselling before testing and during and after the illness to combat the fear and stigma associated with the diagnosis. Another recommendation was that health workers should carry out home visits to patients undergoing home-based care and that COVID-19 treatment should be free of charge.
CONCLUSION
COVID-19 home-based care was associated with fear, anxiety, loneliness, depression, economic loss and stigma. Policymakers should consider various home-based follow-up strategies and strengthen counselling of COVID-19 patients at all stages of care.
Topics: Humans; Uganda; COVID-19; COVID-19 Drug Treatment; Qualitative Research; Home Care Services
PubMed: 38085728
DOI: 10.1371/journal.pone.0295113