Counseling should stress tempered expectations for functional improvement and clarify that “normalizing T” is not a solution for aging. Steer clear of tx solely for those with milder deficits or primary complaints of fatigue or physical limitation alone.
Progesterone selectively increases amygdala reactivity in women. Molecular Psychiatry, 13(3), 325–333.) The Role of GABA−A Receptor Subunits: The mechanism behind this paradoxical reaction may lie in the GABA−A receptor itself. Research suggests that women with PMDD may have an altered sensitivity or function of these receptors. Changes in the specific subunits that make up the GABA−A receptor could lead to a dysfunctional response to allopregnanolone. Instead of the usual inhibitory effect, it might lead to excitation or a lack of inhibition, triggering the emotional dysregulation seen in PMDD.
This is supported by the efficacy of treatments that suppress ovulation or directly block progesterone metabolites. Allopregnanolone in premenstrual dysphoric disorder: why are some women sensitive? Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels. The Journal of Biological Chemistry, 286(9), 6825–6838.) To view or add a comment, sign in The Complexities of MHT/HRT in Neuro-Immune Illness As an Endocrinologist, I frequently manage the care of women with complex neuro-immune conditions—including Dysautonomia, POTS, #MyalgicEncephalomyelitis #MECFS, #SORSHOT (Syndrome of Residual Symptoms of Hypothyroidism on T4), and #MCAS. The Journal of Biological Chemistry, 286(9), 6825–6838.) To view or add a comment, sign in Recent research demonstrates that gender-affirming hormone therapy can significantly alter blood protein profiles in transgender women, aligning them more closely with those of cisgender women. Discuss both the modest benefits and the unexpected risks so patients can make informed choices.
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To view or add a comment, sign in The Complexities of MHT/HRT in Neuro-Immune Illness As an Endocrinologist, I frequently manage the care of women with complex neuro-immune conditions—including Dysautonomia, POTS, #MyalgicEncephalomyelitis #MECFS, #SORSHOT (Syndrome of Residual Symptoms of Hypothyroidism on T4), and #MCAS.
For this cohort, Menopausal Hormone Therapy (MHT/HRT) presents an extreme clinical challenge. Patient intolerance or symptomatic worsening, even with bio-identical treatment, is a common and critical observation that demands a nuanced scientific explanation. We must acknowledge that for a susceptible patient subgroup, sex steroids don't always restore balance.
Counseling should stress tempered expectations for functional improvement and clarify that “normalizing T” is not a solution for aging. Steer clear of tx solely for those with milder deficits or primary complaints of fatigue or physical limitation alone. Discuss both the modest benefits and the unexpected risks so patients can make informed choices. To view or add a comment, sign in The Complexities of MHT/HRT in Neuro-Immune Illness As an Endocrinologist, I frequently manage the care of women with complex neuro-immune conditions—including Dysautonomia, POTS, #MyalgicEncephalomyelitis #MECFS, #SORSHOT (Syndrome of Residual Symptoms of Hypothyroidism on T4), and #MCAS. For this cohort, Menopausal Hormone Therapy (MHT/HRT) presents an extreme clinical challenge.
Patient intolerance or symptomatic worsening, even with bio-identical treatment, is a common and critical observation that demands a nuanced scientific explanation. We must acknowledge that for a susceptible patient subgroup, sex steroids don't always restore balance. Given the starkly higher prevalence of these chronic conditions in women, the critical role of sex hormones in biological vulnerability cannot be overstated.1. Progesterone's Paradoxical Excitation of the Fear Circuit 🧠 While its neurosteroid metabolite, Allopregnanolone, is often hailed as anxiolytic (via GABA potentiation), Progesterone can be uniquely problematic, particularly in patients with pre-existing nervous system hyperarousal (e.g., hyperadrenergic POTS): Amygdala Activation: Progesterone has been shown to selectively increase the reactivity of the Amygdala, the brain's central fear and stress processing centre. This phenomenon may directly explain clinical observations of worsened anxiety, panic attacks, and emotional hyper-vigilance with Progesterone use. Given the starkly higher prevalence of these chronic conditions in women, the critical role of sex hormones in biological vulnerability cannot be overstated.1. Progesterone's Paradoxical Excitation of the Fear Circuit 🧠 While its neurosteroid metabolite, Allopregnanolone, is often hailed as anxiolytic (via GABA potentiation), Progesterone can be uniquely problematic, particularly in patients with pre-existing nervous system hyperarousal (e.g., hyperadrenergic POTS): Amygdala Activation: Progesterone has been shown to selectively increase the reactivity of the Amygdala, the brain's central fear and stress processing centre. This phenomenon may directly explain clinical observations of worsened anxiety, panic attacks, and emotional hyper-vigilance with Progesterone use. Progesterone selectively increases amygdala reactivity in women. Molecular Psychiatry, 13(3), 325–333.) The Role of GABA−A Receptor Subunits: The mechanism behind this paradoxical reaction may lie in the GABA−A receptor itself. Research suggests that women with PMDD may have an altered sensitivity or function of these receptors. Changes in the specific subunits that make up the GABA−A receptor could lead to a dysfunctional response to allopregnanolone. Instead of the usual inhibitory effect, it might lead to excitation or a lack of inhibition, triggering the emotional dysregulation seen in PMDD. This is supported by the efficacy of treatments that suppress ovulation or directly block progesterone metabolites. Allopregnanolone in premenstrual dysphoric disorder: why are some women sensitive?
Antagonist action of progesterone at σ-receptors in the modulation of voltage-gated sodium channels.
💫 Efficacy: Even when antidepressants slightly blunted the intensity of the entheogenic experience, the therapeutic outcomes for depression and anxiety remained significant. In some studies, patients on antidepressants improved as much or more than those who discontinued them. ⚠️ Risks of discontinuation: Forcing patients to stop antidepressants can lead to relapse, withdrawal symptoms, and suicidal ideation — all before entering a psychologically open and vulnerable state. In other words: the “washout” phase may do more harm than the drug combination itself. 🌱 The takeaway: Continuing antidepressants during entheogen-assisted therapy may actually increase accessibility and safety for millions who currently can’t participate in research or treatment.
This isn’t just a pharmacological question — it’s an ethical one. The Journal of Biological Chemistry, 286(9), 6825–6838.) To view or add a comment, sign in The Complexities of MHT/HRT in Neuro-Immune Illness As an Endocrinologist, I frequently manage the care of women with complex neuro-immune conditions—including Dysautonomia, POTS, #MyalgicEncephalomyelitis #MECFS, #SORSHOT (Syndrome of Residual Symptoms of Hypothyroidism on T4), and #MCAS.
| Interaction Type | Dapoxetin | Sildenafil |
|---|---|---|
| Other SSRIs or SNRIs | Increased risk of serotonin syndrome | No significant interaction |
| Nitrates | Contraindicated | Contraindicated |
| Alpha-blockers | Use cautiously, risk of hypotension | Use cautiously, risk of hypotension |
| CYP3A4 Inhibitors | Increased dapoxetin levels | Increased sildenafil levels |
| CYP3A4 Inducers | Reduced efficacy | Reduced sildenafil levels |
The Journal of Biological Chemistry, 286(9), 6825–6838.) To view or add a comment, sign in Recent research demonstrates that gender-affirming hormone therapy can significantly alter blood protein profiles in transgender women, aligning them more closely with those of cisgender women. These changes may influence susceptibility to certain health conditions, including autoimmune diseases and heart disease. The findings highlight the importance of nuanced, long-term health monitoring and suggest that personalized treatment approaches could enhance care for individuals undergoing hormone therapy. This research underscores the adaptability of human biology and the need for healthcare providers to consider both shared and unique health risks in transgender women. To view or add a comment, sign in Recent research demonstrates that gender-affirming hormone therapy can significantly alter blood protein profiles in transgender women, aligning them more closely with those of cisgender women.
🤓Clinical studies remain limited for most substances but early results show reductions in cravings, substance use, and other related outcomes. Definitely worth reading!👍👏😀 To view or add a comment, sign in 𝐆𝐋𝐏-1 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐚𝐧𝐝 𝐓𝐡𝐞𝐢𝐫 𝐄𝐦𝐞𝐫𝐠𝐢𝐧𝐠 𝐑𝐨𝐥𝐞 𝐢𝐧 𝐀𝐥𝐜𝐨𝐡𝐨𝐥 𝐚𝐧𝐝 𝐒𝐮𝐛𝐬𝐭𝐚𝐧𝐜𝐞 𝐔𝐬𝐞 𝐃𝐢𝐬𝐨𝐫𝐝𝐞𝐫𝐬: 𝐀𝐧 𝐄𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐨𝐥𝐨𝐠𝐲 𝐏𝐫𝐢𝐦𝐞𝐫 Very interesting review just published in The Journal of the Endocrine Society by Nirupam Srinivasan and colleagues. To view or add a comment, sign in ICD-10-CM Diagnosis Code Updates Total changes: 252 new codes, 36 deletions, 13 revisions Notable additions by chapter: Chapter 2 (Neoplasms): New codes for Hodgkin lymphoma in remission (e.g., C81.0A–C81.9A) Chapter 4 (Endocrine): Presymptomatic Type 1 diabetes (E10.A-), new obesity classifications (E66.811–E66.813), and MC4R pathway-related obesity (E88.82) Chapter 5 (Mental Disorders): Expanded eating disorder codes including anorexia nervosa subtypes, binge eating disorder, pica, and rumination disorder in adults Chapter 6 (Nervous System): New epilepsy codes (e.g., G40.84 for KCNQ2-related epilepsy), serotonin syndrome (G90.81), and developmental encephalopathy (G93.45) Chapter 9 (Circulatory System): Expanded pulmonary embolism codes (I26.03–I26.96) Chapter 10 (Respiratory System): New codes for nasal valve collapse under acute bronchiolitis (J21) 🛠️ ICD-10-PCS Procedure Code Updates These updates also take effect October 1, 2025, and apply to inpatient procedures through September 30, 2026. To view or add a comment, sign in 💊 Should patients really stop antidepressants before entheogen therapy? A new 2025 review challenges one of the field’s most rigid assumptions.
For decades, clinical trials with psilocybin, LSD, and DMT have required participants to discontinue antidepressants (SSRIs, SNRIs, MAOIs, etc.) weeks before an entheogen session. To “avoid serotonin syndrome” and “preserve the full psychedelic experience.” But the latest scoping review by Tap et al. (2025, Journal of Psychopharmacology) suggests this protocol may be both outdated and harmful. After analyzing 19 human studies across psilocybin, LSD, DMT, and ayahuasca, the authors found that: 🧠 Safety: There’s no robust evidence that taking antidepressants with classic entheogens increases the risk of serotonin toxicity — particularly with psilocybin. Most side effects (headache, mild nausea, temporary increases in blood pressure) were comparable to placebo. To view or add a comment, sign in Here’s what research shows: 🔹 Key Study: A large 2016 study published in European Urology (by researchers from Harvard University) followed more than 30,000 men for almost two decades. They found that: • Men who ejaculated 21 or more times per month had about a 20% lower risk of developing prostate cancer than those who ejaculated 4–7 times per month.
🔹 What counts: Ejaculation frequency includes sex with a partner, masturbation, or nocturnal emissions.
• Men should still get regular prostate screenings as recommended by their doctor. ✅ Summary: Research suggests that around 21 ejaculations per month (roughly 4–5 times per week) is associated with the lowest risk of prostate cancer in men, compared dapoxetine order online with lower frequencies. To view or add a comment, sign in 𝐆𝐋𝐏-1 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐚𝐧𝐝 𝐓𝐡𝐞𝐢𝐫 𝐄𝐦𝐞𝐫𝐠𝐢𝐧𝐠 𝐑𝐨𝐥𝐞 𝐢𝐧 𝐀𝐥𝐜𝐨𝐡𝐨𝐥 𝐚𝐧𝐝 𝐒𝐮𝐛𝐬𝐭𝐚𝐧𝐜𝐞 𝐔𝐬𝐞 𝐃𝐢𝐬𝐨𝐫𝐝𝐞𝐫𝐬: 𝐀𝐧 𝐄𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐨𝐥𝐨𝐠𝐲 𝐏𝐫𝐢𝐦𝐞𝐫 Very interesting review just published in The Journal of the Endocrine Society by Nirupam Srinivasan and colleagues. ✍Alcohol and other substance use disorders (ASUDs) are complex, multifaceted, but treatable medical conditions with widespread medical, psychological, and societal consequences. ✍However, treatment options remain limited, therefore the discovery and development of new treatments for ASUDs is critical.
✍Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently approved for the treatment of type 2 diabetes mellitus, obesity, and obstructive sleep apnea, have recently emerged as potential new pharmacotherapies for ASUDs. ✍Following an overview of the epidemiology, biology, consequences, and treatments of ASUDs, this review provides a summary of the emerging role of GLP-1RAs in the treatment of ASUDs by elucidating their interactions with various neurobiological pathways involved in addiction. ✍It also highlights existing gaps in research, future directions, and broader implications related to the potential use of GLP-1RAs for addiction treatment. 🤓 Very interesting topic and well written paper 🤓Most of the times we talk about alcohol addiction and GLP-1RAs, however the topic si much broader. 🤓 Preclinical studies have consistently demonstrated the potential of GLP-1RAs in reducing the consumption and rewarding properties of alcohol, opioids, nicotine, and psychostimulants. 🔹 Why it may help: More frequent ejaculation may help clear potentially harmful substances from the prostate and reduce inflammation, though the exact biological reason is still being studied. 🔹 Important context: • It’s not a prescription — just a correlation, not proof of cause and effect. • Overall lifestyle (diet, exercise, weight, and not smoking) also strongly affects prostate health. • Men should still get regular prostate screenings as recommended by their doctor. ✅ Summary: Research suggests that around 21 ejaculations per month (roughly 4–5 times per week) is associated with the lowest risk of prostate cancer in men, compared dapoxetine order online with lower frequencies. To view or add a comment, sign in 𝐆𝐋𝐏-1 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐚𝐧𝐝 𝐓𝐡𝐞𝐢𝐫 𝐄𝐦𝐞𝐫𝐠𝐢𝐧𝐠 𝐑𝐨𝐥𝐞 𝐢𝐧 𝐀𝐥𝐜𝐨𝐡𝐨𝐥 𝐚𝐧𝐝 𝐒𝐮𝐛𝐬𝐭𝐚𝐧𝐜𝐞 𝐔𝐬𝐞 𝐃𝐢𝐬𝐨𝐫𝐝𝐞𝐫𝐬: 𝐀𝐧 𝐄𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐨𝐥𝐨𝐠𝐲 𝐏𝐫𝐢𝐦𝐞𝐫 Very interesting review just published in The Journal of the Endocrine Society by Nirupam Srinivasan and colleagues. ✍Alcohol and other substance use disorders (ASUDs) are complex, multifaceted, but treatable medical conditions with widespread medical, psychological, and societal consequences. ✍However, treatment options remain limited, therefore the discovery and development of new treatments for ASUDs is critical. ✍Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently approved for the treatment of type 2 diabetes mellitus, obesity, and obstructive sleep apnea, have recently emerged as potential new pharmacotherapies for ASUDs. ✍Following an overview of the epidemiology, biology, consequences, and treatments of ASUDs, this review provides a summary of the emerging role of GLP-1RAs in the treatment of ASUDs by elucidating their interactions with various neurobiological pathways involved in addiction. ✍It also highlights existing gaps in research, future directions, and broader implications related to the potential use of GLP-1RAs for addiction treatment. 🤓 Very interesting topic and well written paper 🤓Most of the times we talk about alcohol addiction and GLP-1RAs, however the topic si much broader. 🤓 Preclinical studies have consistently demonstrated the potential of GLP-1RAs in reducing the consumption and rewarding properties of alcohol, opioids, nicotine, and psychostimulants.
| Parameter | Dapoxetin | Sildenafil |
|---|---|---|
| Absorption | Rapid, peak 1-2 hours | Rapid, peak 1 hour |
| Bioavailability | Approximately 60-70% | Approximately 40-50% |
| Half-life | About 1 hour | 4-5 hours |
| Metabolism | Liver (cytochrome P450) | Liver (CYP3A4, CYP2C9) |
| Excretion | Urine (main), feces | Feces and urine |
🤓Clinical studies remain limited for most substances but early results show reductions in cravings, substance use, and other related outcomes. Definitely worth reading!👍👏😀 To view or add a comment, sign in 𝐆𝐋𝐏-1 𝐓𝐡𝐞𝐫𝐚𝐩𝐞𝐮𝐭𝐢𝐜𝐬 𝐚𝐧𝐝 𝐓𝐡𝐞𝐢𝐫 𝐄𝐦𝐞𝐫𝐠𝐢𝐧𝐠 𝐑𝐨𝐥𝐞 𝐢𝐧 𝐀𝐥𝐜𝐨𝐡𝐨𝐥 𝐚𝐧𝐝 𝐒𝐮𝐛𝐬𝐭𝐚𝐧𝐜𝐞 𝐔𝐬𝐞 𝐃𝐢𝐬𝐨𝐫𝐝𝐞𝐫𝐬: 𝐀𝐧 𝐄𝐧𝐝𝐨𝐜𝐫𝐢𝐧𝐨𝐥𝐨𝐠𝐲 𝐏𝐫𝐢𝐦𝐞𝐫 Very interesting review just published in The Journal of the Endocrine Society by Nirupam Srinivasan and colleagues. To view or add a comment, sign in ICD-10-CM Diagnosis Code Updates Total changes: 252 new codes, 36 deletions, 13 revisions Notable additions by chapter: Chapter 2 (Neoplasms): New codes for Hodgkin lymphoma in remission (e.g., C81.0A–C81.9A) Chapter 4 (Endocrine): Presymptomatic Type 1 diabetes (E10.A-), new obesity classifications (E66.811–E66.813), and MC4R pathway-related obesity (E88.82) Chapter 5 (Mental Disorders): Expanded eating disorder codes including anorexia nervosa subtypes, binge eating disorder, pica, and rumination disorder in adults Chapter 6 (Nervous System): New epilepsy codes (e.g., G40.84 for KCNQ2-related epilepsy), serotonin syndrome (G90.81), and developmental encephalopathy (G93.45) Chapter 9 (Circulatory System): Expanded pulmonary embolism codes (I26.03–I26.96) Chapter 10 (Respiratory System): New codes for nasal valve collapse under acute bronchiolitis (J21) 🛠️ ICD-10-PCS Procedure Code Updates These updates also take effect October 1, 2025, and apply to inpatient procedures through September 30, 2026. To view or add a comment, sign in 💊 Should patients really stop antidepressants before entheogen therapy? A new 2025 review challenges one of the field’s most rigid assumptions. For decades, clinical trials with psilocybin, LSD, and DMT have required participants to discontinue antidepressants (SSRIs, SNRIs, MAOIs, etc.) weeks before an entheogen session. To “avoid serotonin syndrome” and “preserve the full psychedelic experience.” But the latest scoping review by Tap et al. (2025, Journal of Psychopharmacology) suggests this protocol may be both outdated and harmful. After analyzing 19 human studies across psilocybin, LSD, DMT, and ayahuasca, the authors found that: 🧠 Safety: There’s no robust evidence that taking antidepressants with classic entheogens increases the risk of serotonin toxicity — particularly with psilocybin. Most side effects (headache, mild nausea, temporary increases in blood pressure) were comparable to placebo.
| Drug Name | Class | Mechanism of Action | Common Uses |
|---|---|---|---|
| Dapoxetin | Selective Serotonin Reuptake Inhibitor (SSRI) | Increases serotonin levels in the brain | Premature ejaculation treatment |
| Sildenafil | Phosphodiesterase type 5 (PDE5) inhibitor | Enhances blood flow by relaxing smooth muscles | Erectile dysfunction |
| Tadalafil | PDE5 inhibitor | Longer duration of action compared to sildenafil | Erectile dysfunction, BPH |
| Dapoxetin | SSRI - Short-acting | Rapid onset for premature ejaculation | Premature ejaculation |
| Vardenafil | PDE5 inhibitor | Similar to sildenafil, rapid onset | Erectile dysfunction |
| Sildenafil | PDE5 inhibitor | Vasodilation effect on penile blood vessels | Erectile dysfunction |
💫 Efficacy: Even when antidepressants slightly blunted the intensity of the entheogenic experience, the therapeutic outcomes for depression and anxiety remained significant. In some studies, patients on antidepressants improved as much or more than those who discontinued them. ⚠️ Risks of discontinuation: Forcing patients to stop antidepressants can lead to relapse, withdrawal symptoms, and suicidal ideation — all before entering a psychologically open and vulnerable state. In other words: the “washout” phase may do more harm than the drug combination itself. 🌱 The takeaway: Continuing antidepressants during entheogen-assisted therapy may actually increase accessibility and safety for millions who currently can’t participate in research or treatment.
This isn’t just a pharmacological question — it’s an ethical one.
These changes may influence susceptibility to certain health conditions, including autoimmune diseases and heart disease. The findings highlight the importance of nuanced, long-term health monitoring and suggest that personalized treatment approaches could enhance care for individuals undergoing hormone therapy. This research underscores the adaptability of human biology and the need for healthcare providers to consider both shared and unique health risks in transgender women. To view or add a comment, sign in Recent research demonstrates that gender-affirming hormone therapy can significantly alter blood protein profiles in transgender women, aligning them more closely with those of cisgender women. To view or add a comment, sign in Here’s what research shows: 🔹 Key Study: A large 2016 study published in European Urology (by researchers from Harvard University) followed more than 30,000 men for almost two decades.
They found that: • Men who ejaculated 21 or more times per month had about a 20% lower risk of developing prostate cancer than those who ejaculated 4–7 times per month. 🔹 What counts: Ejaculation frequency includes sex with a partner, masturbation, or nocturnal emissions. 🔹 Why it may help: More frequent ejaculation may help clear potentially harmful substances from the prostate and reduce inflammation, though the exact biological reason is still being studied. 🔹 Important context: • It’s not a prescription — just a correlation, not proof of cause and effect. • Overall lifestyle (diet, exercise, weight, and not smoking) also strongly affects prostate health.