Newly joined member here but have been lurking for 6mo learning and absorbing as much as I can here. Appreciate what an incredible resource this site is and the members contributing. I fell into the trap of eating poorly, drinking often, and spiraling my weight out of control in the last few years. Blood work awful terrible lipids etc. Testosterone low. Decided to go all out to fix this.
DR put me on Tirzepatide 5mg weekly injection (did a month at 2.5mg then ramped and have stayed at 5mg for 4 more months and losing consistently). Almost IMMEDIATELY on starting the Tirzepatide I had a drastic change from being able to finish in the bedroom pretty rapidly (sometimes thinking it was ALMOST PE as I got a little too excited lol) to the exact opposite and now I can go forever and not finish unless I really push to the maximum. Sometimes it results in going for ages and getting too sweaty and exhausted and giving up. I never really thought this could be a problem but once experiencing it it can be super frustrating.
I don't want to quit the Tirzepatide as I'm down from 252 lbs to 209 lbs now in 5 months and continuing to lose. After explaining all this to my DR and seeing Testosterone in the 200s on multiple blood tests fasted in the morning we started Enclomiphene 25mg daily. This has shot my energy and general libido sky high over the last 3 months and I've never felt better in my entire life overall. The one nagging issue is this extremely delayed or inability to finish. It's almost worse now in that I basically want to hook up every day now...
I'm going through some of the options and trying to figure out what might make sense...
DR suggested adding AI (Anastrozole) at 0.125mg 2x to 3x a week but I've seen significant warnings about crashing E2 so I'm a bit hesitant there. I also have seen some stuff that Enclomiphene is blocking some of the estrogen receptors anyways so a slightly higher E2 shouldn't be problematic?
Cabergoline? This seems to be related to high prolactin though and I don't have that?
Current Labs (Last week after 3mo Enclomiphene 25mg daily):
Testosterone 950
Free T 25.0
LH 14.0
FSH 7.9
SHBG 23.2
Prolactin 8.5
E2(Estradiol Sensitive) 46.1
IGF-1 122
A1C 5.2%
On top of this my cholesterol has dropped from 220 to 160 and my triglycerides from 300 to 177. Feeling amazing in the gym!
There is quite a bit of reports of anhedonia when taking a GLP-1 as well which I can't say I notice otherwise. DR wants to try lowering E2 but my concern is that the problem seems linked to the GLP-1 to me and not the rise in E2. I would appreciate any and all insight and suggestions on this from the EM community. Thanks everyone!
DR wants to try lowering E2 but my concern is that the problem seems linked to the GLP-1 to me and not the rise in E2. I would appreciate any and all insight and suggestions on this from the EM community.
Newly joined member here but have been lurking for 6mo learning and absorbing as much as I can here. Appreciate what an incredible resource this site is and the members contributing. I fell into the trap of eating poorly, drinking often, and spiraling my weight out of control in the last few years. Blood work awful terrible lipids etc. Testosterone low. Decided to go all out to fix this.
DR put me on Tirzepatide 5mg weekly injection (did a month at 2.5mg then ramped and have stayed at 5mg for 4 more months and losing consistently). Almost IMMEDIATELY on starting the Tirzepatide I had a drastic change from being able to finish in the bedroom pretty rapidly (sometimes thinking it was ALMOST PE as I got a little too excited lol) to the exact opposite and now I can go forever and not finish unless I really push to the maximum. Sometimes it results in going for ages and getting too sweaty and exhausted and giving up. I never really thought this could be a problem but once experiencing it it can be super frustrating.
I don't want to quit the Tirzepatide as I'm down from 252 lbs to 209 lbs now in 5 months and continuing to lose. After explaining all this to my DR and seeing Testosterone in the 200s on multiple blood tests fasted in the morning we started Enclomiphene 25mg daily. This has shot my energy and general libido sky high over the last 3 months and I've never felt better in my entire life overall. The one nagging issue is this extremely delayed or inability to finish. It's almost worse now in that I basically want to hook up every day now...
I'm going through some of the options and trying to figure out what might make sense...
DR suggested adding AI (Anastrozole) at 0.125mg 2x to 3x a week but I've seen significant warnings about crashing E2 so I'm a bit hesitant there. I also have seen some stuff that Enclomiphene is blocking some of the estrogen receptors anyways so a slightly higher E2 shouldn't be problematic?
Cabergoline? This seems to be related to high prolactin though and I don't have that?
Current Labs (Last week after 3mo Enclomiphene 25mg daily):
Testosterone 950
Free T 25.0
LH 14.0
FSH 7.9
SHBG 23.2
Prolactin 8.5
E2(Estradiol Sensitive) 46.1
IGF-1 122
A1C 5.2%
On top of this my cholesterol has dropped from 220 to 160 and my triglycerides from 300 to 177. Feeling amazing in the gym!
There is quite a bit of reports of anhedonia when taking a GLP-1 as well which I can't say I notice otherwise. DR wants to try lowering E2 but my concern is that the problem seems linked to the GLP-1 to me and not the rise in E2. I would appreciate any and all insight and suggestions on this from the EM community. Thanks everyone!
Newly joined member here but have been lurking for 6mo learning and absorbing as much as I can here. Appreciate what an incredible resource this site is and the members contributing. I fell into the trap of eating poorly, drinking often, and spiraling my weight out of control in the last few years. Blood work awful terrible lipids etc. Testosterone low. Decided to go all out to fix this.
DR put me on Tirzepatide 5mg weekly injection (did a month at 2.5mg then ramped and have stayed at 5mg for 4 more months and losing consistently). Almost IMMEDIATELY on starting the Tirzepatide I had a drastic change from being able to finish in the bedroom pretty rapidly (sometimes thinking it was ALMOST PE as I got a little too excited lol) to the exact opposite and now I can go forever and not finish unless I really push to the maximum. Sometimes it results in going for ages and getting too sweaty and exhausted and giving up. I never really thought this could be a problem but once experiencing it it can be super frustrating.
I don't want to quit the Tirzepatide as I'm down from 252 lbs to 209 lbs now in 5 months and continuing to lose. After explaining all this to my DR and seeing Testosterone in the 200s on multiple blood tests fasted in the morning we started Enclomiphene 25mg daily. This has shot my energy and general libido sky high over the last 3 months and I've never felt better in my entire life overall. The one nagging issue is this extremely delayed or inability to finish. It's almost worse now in that I basically want to hook up every day now...
I'm going through some of the options and trying to figure out what might make sense...
DR suggested adding AI (Anastrozole) at 0.125mg 2x to 3x a week but I've seen significant warnings about crashing E2 so I'm a bit hesitant there. I also have seen some stuff that Enclomiphene is blocking some of the estrogen receptors anyways so a slightly higher E2 shouldn't be problematic?
Cabergoline? This seems to be related to high prolactin though and I don't have that?
Current Labs (Last week after 3mo Enclomiphene 25mg daily):
Testosterone 950
Free T 25.0
LH 14.0
FSH 7.9
SHBG 23.2
Prolactin 8.5
E2(Estradiol Sensitive) 46.1
IGF-1 122
A1C 5.2%
On top of this my cholesterol has dropped from 220 to 160 and my triglycerides from 300 to 177. Feeling amazing in the gym!
There is quite a bit of reports of anhedonia when taking a GLP-1 as well which I can't say I notice otherwise. DR wants to try lowering E2 but my concern is that the problem seems linked to the GLP-1 to me and not the rise in E2. I would appreciate any and all insight and suggestions on this from the EM community. Thanks everyone!
Tough question. Your T:E ratio is 20.6 which is on the high end of the range. So it may be that your E2 is actually slightly low in relation to your T. If you have lost a lot of fat mass you may be aromatizing less which could be the reason. On the other hand, your E2 is high in an absolute sense, and I don't think it is clearly known whether the T:E ratio or the absolute E2 level is most critical for orgasm. These things are complicated and it is a balancing act without clear answers from labs alone.
When did you start TRT in relation to Tirzepatide?
I do think sometimes a little trial and error may be necessary to see what works, and that may be what your doc is thinking. He/she is talking about starting with a very low dose of anastrazole at 0.125mg so that would not "crash" your E2. Typical dose is 0.5-1.0 mg. Personally, I think if this is causing you a problem you have to start somewhere. If no improvement on low dose AI, and there certainly may not be, then you've kind of ruled out a elevated E2 effect as the cause.
As far as Prolactin, I'm not terribly familiar with expected levels and how to approach that issue, other than to say some experts suspect that problems that have been blamed on E2 may actually be due to PRL.
@Nelson Vergel Thanks for amazingly fast response. I've been reading your recent posts on Anorgasmia which has been super helpful. Just for clarification, your comment on prolactin is that directed towards the cabergoline? I'm pretty darn confident the Anorgasmia (and general reduction in sensitivity and ability to finish) originated from the GLP-1 (Tirzepatide) and not from the Enclomiphene/jump in T or E2 as I started the Tirzepatide a few months before the hormone therapy and it was prevalent then...
I've seen stuff about GLPs effecting dopamine and just looking if there may be some solutions to fix this other than stopping the GLP-1. Seems like maybe something that boosts dopamine might help?
Tough question. Your T:E ratio is 20.6 which is on the high end of the range. So it may be that your E2 is actually slightly low in relation to your T. If you have lost a lot of fat mass you may be aromatizing less which could be the reason. However, these things are complicated and it is a balancing act without clear answers from labs alone.
When did you start TRT in relation to Tirzepatide?
I do think sometimes a little trial and error may be necessary to see what works, and that may be what your doc is thinking.
Tirzepatide started in July and the issues with a big drop in sensitivity and being able to finish corresponded to that. When I raised those issues to DR that's actually one of the main reasons he started checking test levels and then suggested TRT. The TRT protocol increased my desire to hook up drastically and generally been a huge energy boost it's just hard to finish what I start lol
Tirzepatide started in July and the issues with a big drop in sensitivity and being able to finish corresponded to that. When I raised those issues to DR that's actually one of the main reasons he started checking test levels and then suggested TRT. The TRT protocol increased my desire to hook up drastically and generally been a huge energy boost it's just hard to finish what I start lol
I wonder if there is a direct effect of Tirzepatide on the brain that could interact negatively with the Test. I am on both of these as well and have recently had a similar issue, but only after starting the Test. I will say that for myself, my wife and my daughter - we each started at 2.5 mg Tirzepatide and stayed on that dose without increasing. Each of us rapidly lost weight without need to increase dose. I personally lost 11 lbs (6.58% of my body weight) in the first month on 2.5 mg. Staying on that dose I continued to lose and over the next month had a total weight loss of 10.3% baseline over just 2 months (17 lbs). At that point I decreased to 1.25 mg Tirzepatide and have remained now another month on that dose and have been maintaining. I have not gained anything back, though I am logging calories and protein and being careful, but it has been easy without the food noise, even on 1.25 mg. After another month or so I plan to stop the Tirzepatide and try to maintain without it. I am at my goal weight for the past month.
Lower doses of Tirzepatide work very well. For obesity the higher doses may be necessary. Microdosing is highly effective for those with BMI higher than they would like but not in the obese category.
I wonder if there is a direct effect of Tirzepatide on the brain that could interact negatively with the Test. I am on both of these as well and have recently had a similar issue, but only after starting the Test. I will say that for myself, my wife and my daughter - we each started at 2.5 mg Tirzepatide and stayed on that dose without increasing. Each of us rapidly lost weight without need to increase dose. I personally lost 11 lbs (6.58% of my body weight) in the first month on 2.5 mg. Staying on that dose I continued to lose and over the next month had a total weight loss of 10.3% baseline over just 2 months (17 lbs). At that point I decreased to 1.25 mg Tirzepatide and have remained now another month on that dose and have been maintaining. I have not gained anything back, though I am logging calories and protein and being careful, but it has been easy without the food noise, even on 1.25 mg.
Lower doses of Tirzepatide work very well. For obesity the higher doses may be necessary. Microdosing is highly effective for those with BMI higher than they would like but not in the obese category.
There are so many reports of blunted dopamine / "anhedonia" from the tirzepatide for sure. Did microdosing improve it for you? I have seen so many people complaining about loss of libido or penile sensitivity or orgasm issues on the tirzepatide but not really seen anyone suggesting or having found any fixes for this. Can't really find any data on microdosing related to this issue nor trying any dopamine related meds like cabergoline connected to this specifically so I'm at a real loss as to what to experiment with!
There are so many reports of blunted dopamine / "anhedonia" from the tirzepatide for sure. Did microdosing improve it for you? I have seen so many people complaining about loss of libido or penile sensitivity or orgasm issues on the tirzepatide but not really seen anyone suggesting or having found any fixes for this. Can't really find any data on microdosing related to this issue nor trying any dopamine related meds like cabergoline connected to this specifically so I'm at a real loss as to what to experiment with!
Honestly, for me Tirzepatide was a life changer. I lost weight and fat so quickly and easily, it really improved my overall mood and outlook on life dramatically. The boost it gave me incentivized me to start working out in a serious way, and I've never been like that. I began to dress better, more fitted clothes, etc.
So Tirzepatide definitely did not have the effect of anhedonia on me - the opposite. My issue was that when I subsequently started TRT (also incentivized by the postive effects of the GLP1), that's when I noticed an effect on my sexual function. Not as dramatic as what you have described, but still definitely lowered libido and more difficutly with orgasm. I expected the opposite effect, so I'm unsure what happened. I have also been taking HCG with the TRT, and some have suggested this could be the cause. Another suggestion was that it was just the sudden changes in hormone levels may take time to adjust to, which makes sense. I suspected E2 as another potential culprit. I took a microdose of anastrazole for it yesterday as a test dose, and I think it may be having a postive effect already, but too early to know for sure, maybe wishful thinking. Ultimately, if as needed small doses of anastrazole doesn't help, and it doesn't just improve on its own, I'll stop HCG for a while and see if that helps.
Honestly, for me Tirzepatide was a life changer. I lost weight and fat so quickly and easily, it really improved my overall mood and outlook on life dramatically. The boost it gave me incentivized me to start working out in a serious way, and I've never been like that. I began to dress better, more fitted clothes, etc.
So Tirzepatide definitely did not have the effect of anhedonia on me - the opposite. My issue was that when I subsequently started TRT (also incentivized by the postive effects of the GLP1), that's when I noticed an effect on my sexual function. Not as dramatic as what you have described, but still definitely lowered libido and more difficutly with orgasm. I expected the opposite effect, so I'm unsure what happened. I have also been taking HCG with the TRT, and some have suggested this could be the cause. Another suggestion was that it was just the sudden changes in hormone levels may take time to adjust to, which makes sense. I suspected E2 as another potential culprit. I took a microdose of anastrazole for it yesterday as a test dose, and I think it may be having a postive effect already, but too early to know for sure, maybe wishful thinking. Ultimately, if as needed small doses of anastrazole doesn't help, and it doesn't just improve on its own, I'll stop HCG for a while and see if that helps.
Same here on the Tirzepatide. Closing in on 50 pounds down now and I share very similar feelings to you. My overall life and happiness has never been higher. I started finding some actual enjoyment out of the gym and sauna. This stuff is so complicated and tricky. My overall interest in sex is way up after the testosterone boost it's solely the finishing part that has been difficult for me. Let me know how the anastrazole goes. How small of a dose are you trying?
Same here on the Tirzepatide. Closing in on 50 pounds down now and I share very similar feelings to you. My overall life and happiness has never been higher. I started finding some actual enjoyment out of the gym and sauna. This stuff is so complicated and tricky. My overall interest in sex is way up after the testosterone boost it's solely the finishing part that has been difficult for me. Let me know how the anastrazole goes. How small of a dose are you trying?
The TRT clinic gave me 10 1mg tablets and suggesed I take 1/2 tablet (.5 mg) Mon and Thurs with my TC only if I am having symptoms of high E2, and the list of symptoms they gave me included low libido but nothing specific regarding orgasm (that would be kinda weird to put on the form!).
But I wanted to try .25 mg first since it is pretty potent and I wanted to start slow and see. I tried to cut the pill into quarters, but probably wasn't exact as some of the pieces ended up a bit larger than others. So somewhere around .25 mg...
I've had no noticeable side effects (took it yesterday morning).
As I said, it may be helping, I'll keep ya posted.
It seems pretty safe to say the GLP-1 is causing the issues. As with everything in life, there are tradeoffs between pros and cons so the key is to find the optimal balance that gives the most benefits with minimal(or at least acceptable) unwanted sides. Does the inability to finish occur regardless of how long you go without sex? Before trt I used to finish pretty quickly, but now on trt and HCG I can control it to a large extent and only finish when I focus and want to be done. Over the last few years I have had some occasional bouts of requiring a longer time to finish, but even during those periods if I went a few days without sex I’d finish within 5 minutes or so. It seems you’re getting lots of benefits from both of your medications, so perhaps it’s just as simple as finding the right timeframes for sex that allow you get it as frequently as possible while still being able to enjoy and finish in a reasonable amount of time. For me the time of day seems to make a difference as well, so that may be another aspect to consider. There could be other supplements that could help, but I’m not as familiar with that aspect other than HCG. Plus for every new thing you introduce you add to the complexity and have to consider another thing to weigh the pros and cons on.
Glad to hear you’re moving in the right direction though, and welcome to the club of all the members here doing a balancing act to get the most of life.
It would be too easy to change one thing, get off the Tirz for 30 days and see how you feel.
Anytime I've had anorgasma(?) it was because through supplements I was altering that brain chemistry with serotonin or Dopamine and so forth, GABA, 5HTP and that stuff. That inability to finish was brutal for me. I quit overtly tampering with my mind and it resolved itself. I know this is some generalities.
The obvious answer here is to gradually reduce the dose of tirzepatide, until you find a dose that controls your weight without making climax impossible. Like TRT, a series of dosage adjustments are typically required with GLP-1 medications to reach an optimal state of benefits vs. side effects. It sounds as though you've not even attempted the necessary effort of fine-tuning dosage yet.
Interesting connection between GLP-1 agonists and dopamine signaling. Most studies (albeit some are mice studies) indicate that GLP-1 agonists actually increase dopamine signaling. This would appear to be counter to what the OP has alleged as the culprit for the anorgasmia, or delayed orgasm. From someone who has struggled with this for years, I can definitely attest to the dopamine connection as being one of several factors that can cause this condition. For me, selegiline was the final fix. There are other alternatives as well, but selegiline cured it.
It would be easy to determine if it is indeed the Tirzepatide. Since it is a weekly injection, just skip a week or two and see if it resolves. Although it could take up to 30 days for it to completely clear.
Some good info on GLP-1 agonists relation to dopamine signaling:
GLP-1 (glucagon-like peptide-1) medications can increase dopamine levels in the brain, (This is important as it affects brain levels of dopamine and not just digestive levels) which may help reduce cravings and impulsive eating behaviors. This effect is particularly beneficial for individuals
struggling with obesity, as it can enhance motivation for healthy habits and improve appetite control.
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Stanford University
Overview of GLP-1 and Dopamine
GLP-1 (glucagon-like peptide-1) is a hormone that plays a significant role in regulating appetite and blood sugar levels. Recent research has highlighted its effects on the brain's dopamine system, which is crucial for motivation and reward.
How GLP-1 Affects Dopamine Levels
Mechanisms of Action
Dopamine Release: GLP-1 receptor agonists (GLP-1RAs) can enhance dopamine signaling in the brain. This is important because dopamine is linked to feelings of pleasure and reward.
Appetite Regulation: By influencing dopamine levels, GLP-1RAs help control appetite and reduce cravings, particularly for high-calorie foods. This can be beneficial for individuals struggling with obesity or food addiction.
Benefits for Addiction Treatment
Reducing Cravings: GLP-1 medications may help decrease cravings and impulsive eating behaviors by correcting dopamine imbalances. This is especially useful for those whose overeating is driven by low dopamine levels.
Potential in Substance Use Disorders: Research suggests that GLP-1RAs could be effective in treating various substance use disorders by modulating the brain's reward pathways, potentially reducing drug-seeking behavior and relapse rates.
Conclusion
GLP-1 has a significant impact on dopamine levels, influencing both appetite control and the management of addictive behaviors. Its ability to enhance dopamine signaling presents a promising avenue for treating obesity and addiction-related disorders.
We find that the peripheral administration of 1 mg/kg GLP-1 agonist semaglutide impacts on food reward-seeking and VTA dopamine signaling during a Pavlovian sucrose conditioning paradigm. Semaglutide reduced the number of sucrose rewards and licks in the task. At the same time, semaglutide increased the VTA dopamine neuron activity during sucrose collection, independent of task performance as mice without drug-induced reduction in reward-seeking showed increased neuronal activity during reward consumption. In contrast, the VTA dopamine neuron activity during cue was not altered by semaglutide. We conclude that semaglutide reduced appetite and reward-seeking while it increased VTA dopamine neuron activity during reward consumption.
By investigating semaglutides' effect on a second-to-second time scale, we found it to increase VTA dopamine activity during reward collection but not during cue. This contrasts with a previous study that found decreased VTA dopamine activity during a reward-predictive cue after exendin-4 application in the ventricle (Konanur et al., 2020). Also from other studies using other GLP-1 analogs, we expected rather decreased than increased dopamine levels after semaglutide (Egecioglu et al., 2013a, 2013bFortin and Roitman, 2017; Reddy et al., 2016; Sørensen et al., 2015; Vallöf et al., 2016, 2019). The direct administration of Exendin-4 to the brain, compared to intraperitoneal administration may explain the difference in cue-associated dopaminergic activity. Studies on GLP-1R binding sites and c-fos activation after peripheral semaglutide did not find evidence for direct access to the midbrain (Gabery et al., 2020; Hansen et al., 2021), while exendin-4 does (Hernandez et al., 2018). One interpretation for the different impact of exendin-4 compared to semaglutide on dopamine signaling is that semaglutide indirectly activates dopamine neurons via nuclei that are close to the brain's circumventricular organs, such as the NTS, arcuate nucleus of the hypothalamus (ARC) or lateral septum.
We found that semaglutide decreased chow intake while increasing VTA dopamine activity during reward collection but not during the cue. Dopamine is known to impact on different aspects of feeding and food-seeking. Dopamine stimulants such as amphetamine and methylphenidate exert anorexigenic effects (Efron et al., 1997; Sanghvi et al., 1975), while decreased dopamine levels are associated with increased food intake (Cordeira et al., 2010; Verhagen et al., 2009). Additionally, dopamine-deficient mice stop eating, which could be reversed after injecting L-DOPA (Zhou and Palmiter, 1995). A different pattern arises when studying food-seeking, as temporarily inhibiting VTA dopamine neurons reduced food-seeking (Chang et al., 2016; Van Zessen et al., 2021), while excitation of these neurons increased food-seeking behaviors and prevented extinction (Pan et al., 2021; Steinberg et al., 2013). In dopamine-transporter knockouts, which have higher baseline dopamine levels, motivation to obtain food reward is increased without impacting on Pavlovian conditioning (Cagniard et al., 2006). In our Pavlovian experiment, semaglutide increased dopamine activity during reward, decreased food intake and reduced reward seeking. This challenges the current hypothesis on the causality between dopamine activity and food-seeking behaviors. Processes underlying reward cues and consumption are independent processes and it remains to be determined how they impact on food-seeking.
Additionally, dopamine is also associated with liking and saliency of rewards. In our study, the 'liking' of sucrose, as measured by the number of licks in the first bout of reward collection (Johnson, 2018), remained unchanged after semaglutide administration. This suggests that semaglutide does not alter 'liking,' even though the motivation to acquire the reward is reduced, and dopamine activity is increased. One theory is that the VTA DA activity during reward collection is related to salience (Schultz, 2016), making the reward more noticeable after semaglutide.
Earlier studies suggest semaglutide cannot directly access the midbrain but can assess brain areas such as the NTS, ARC or lateral septum (Gabery et al., 2020; Hansen et al., 2021; Jensen et al., 2018). These areas are previously related to influence dopamine signaling and reward-related behaviors. GLP-1R agonists applied in the NTS affected dopamine signaling and diminished reward-seeking behaviors (Alhadeff et al., 2012; Richard et al., 2015; Vallöf et al., 2019). Semaglutide was found to reduce the activity of the ARC and diminish chow intake (Ghidewon et al., 2022). The lateral septum projects to the VTA and is involved in valence and goal-directed behaviors (Wirtshafter and Wilson, 2021). GLP-1 agonists in the lateral septum suppress motivation for food and alcohol reinforcement (Terrill et al., 2019). Thus, there are several pathways via which peripherally administered semaglutide could impact VTA dopamine responsivity. Further studies should reveal via which pathway the VTA dopamine activity is altered.
Semaglutide decreased total sucrose intake during the session. This is consistent with previous literature showing that semaglutide and other GLP-1R agonists reduced palatable food intake, such as chocolate (Gabery et al., 2020). In addition, studies on participants with obesity have shown that semaglutide diminished the preference for energy-dense foods (Blundell et al., 2017). The reduction in sucrose intake was only present after injection of the 1 mg/kg dose, while chow intake was reduced already with a 0.1 mg/kg dose, possibly due to larger quantity of chow provided, compared to the limited amount of sucrose (+-10 kcal in chow vs. 0.4 kcal in the sucrose) that did not satiate.
This study has several limitations. Firstly, high doses of GLP-1 agonists, including semaglutide, can induce nausea and malaise-like symptoms (Kanoski et al., 2012; O'Neil et al., 2018). Although we did not find any malaise signs, we cannot exclude that it may have influenced our findings. Additionally, we conducted our experiments with food-restricted, lean mice to ensure high motivation for sucrose. It would be interesting to repeat the experiments in an ad libitum-fed state and/or overweight mice to determine whether this mechanism also plays a role in a satiated or obesogenic state. Thirdly, we provided little portions of sucrose (8 μl) to keep the mice motivated throughout the task. These quantities are unlikely to be satiating and may explain why lower doses of semaglutide we tested did not reduce task performance while suppressing food intake after the Pavlovian session. Lastly, we determined the effect of semaglutide starting 15 min following intraperitoneal injection, which is rather fast. Although we cannot exclude that semaglutide effects develop over later periods, we believe that an intraperitoneal injection results in rapid distribution, which is confirmed by its effects on motivation and cue-induced dopamine signaling.
In conclusion, a high dose of semaglutide decreased motivation for sucrose, while dopamine activity during reward collection increased. Future research should investigate the underlying mechanisms that mediate these effects. Overall, our study contributes to understanding the GLP-1R agonist semaglutide on reward-related behaviors and neuronal signaling in mice.
Buspirone works best for females. As an anxiolytic medication, it can have a calming effect which can counter the male sexual response. If the condition is anxiety related, it may be a good option for some males.
I have used it in the past. It's a great way to lower anxiety, but I would rather chill and read a book than have sex. Just my experience...
The TRT clinic gave me 10 1mg tablets and suggesed I take 1/2 tablet (.5 mg) Mon and Thurs with my TC only if I am having symptoms of high E2, and the list of symptoms they gave me included low libido but nothing specific regarding orgasm (that would be kinda weird to put on the form!).
But I wanted to try .25 mg first since it is pretty potent and I wanted to start slow and see. I tried to cut the pill into quarters, but probably wasn't exact as some of the pieces ended up a bit larger than others. So somewhere around .25 mg...
I've had no noticeable side effects (took it yesterday morning).
As I said, it may be helping, I'll keep ya posted.
It's best to avoid AI's entirely, but if you are going to try it remember a little goes a long way. Try .25 sublingually (under the tongue) anastrozole doesn't have much of a taste and it works faster taken sublingually. Use it on demand only as symptoms appear. If it doesn't help within a few days, discontinue it.
If it does help, only use it until you determine what is causing the spike. Best to find the cause than treat the symptoms with such a potentially harmful drug.
Predict estradiol, DHT, and free testosterone levels based on total testosterone
⚠️ Medical Disclaimer
This tool provides predictions based on statistical models and should NOT replace professional medical advice.
Always consult with your healthcare provider before making any changes to your TRT protocol.
ℹ️ Input Parameters
Normal range: 300-1000 ng/dL
Predicted Hormone Levels
Enter your total testosterone value to see predictions
Results will appear here after calculation
Understanding Your Hormones
Estradiol (E2)
A form of estrogen produced from testosterone. Important for bone health, mood, and libido.
Too high can cause side effects; too low can affect well-being.
DHT
Dihydrotestosterone is a potent androgen derived from testosterone. Affects hair growth,
prostate health, and masculinization effects.
Free Testosterone
The biologically active form of testosterone not bound to proteins.
Directly available for cellular uptake and biological effects.
Scientific Reference
Lakshman KM, Kaplan B, Travison TG, Basaria S, Knapp PE, Singh AB, LaValley MP, Mazer NA, Bhasin S. The effects of injected testosterone dose and age on the conversion of testosterone to estradiol and dihydrotestosterone in young and older men. J Clin Endocrinol Metab. 2010 Aug;95(8):3955-64.
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