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BUZZ-Lipocine rises on licensing deal for testosterone therapy in US, Canada

** Shares of drug developer Lipocine LPCN.O rise 6.5% to $4.1 premarket

** Co enters into license agreement with Verity Pharma to market its testosterone replacement therapy, Tlando, in the United States and Canada

** Under terms of the deal, co to receive a license fee of $11 million

** Co to also receive up to $259 mln in development and commercial sales milestones

** Under the agreement, Verity Pharma will be responsible for regulatory and marketing obligations in the U.S. and Canada, and all further development of the therapy

** LPCN will retain all rights to the Tlando franchise for territories outside the U.S. and Canada

** Tlando was approved by the U.S. FDA in 2022 as an oral testosterone replacement therapy in adult males for conditions associated with a deficiency or absence of endogenous testosterone

** Stock fell 58.1% in the last 12 months

Reporting by Sneha S K

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Lipocine rises on licensing deal for testosterone therapy in US, Canada - XM

Testosterone isnt just a sex hormone. In men, it plays an important role in many other systems in the body including the heart. And when testosterone levels are abnormal, the heart can experience issues.

The strongest evidence is that abnormally low testosterone is not good cardiovascularly, says Geoff Werstuck, Ph.D., a professor of medicine at McMaster University who specializes in heart health.

In the mid-1980s, scientists measured the testosterone levels of 794 older men, and followed them for the next two decades. The results, published in 2008 in the Journal of Clinical Endocrinology and Metabolism, found that men with the lowest testosterone levels were 38% more likely to die of a cardiovascular event like a stroke or heart attack.

In another analysis, Belgian researchers aggregated results from 19 different studies on testosterone and heart health. They found that men over 70 who had high testosterone were 16% less likely to experience a cardiovascular event than men with low T.

Why do we see this relationship between testosterone and heart health? Scientists arent sure. These population studies dont necessarily show that low testosterone causes cardiovascular problems. It could be that low T is simply a symptom of poor overall health, or, as an article published in the journal Evolution, Medicine, and Public Health theorized, it could caused by another condition that tends to occur alongside heart problems. For example, heart disease is often associated with higher body fat, which in turn can lower testosterone levels.

That said, some studies do suggest a more direct relationship between testosterone and heart problems. Werstuck conducts most of his research in mice, and has found that when mice are castrated, they quickly begin showing signs of atherosclerosis hardening of the arteries that can contribute to heart problems.

We see similar patterns in men treated with androgen deprivation therapy, a treatment for prostate cancer that forces the body to produce very little testosterone. In a 2001 study comparing 26,570 men undergoing this therapy to 46,626 men with prostate cancer who didnt receive it, men receiving androgen deprivation therapy were 16% more likely to have coronary heart disease and 11% more likely to have a heart attack.

One hypothesis as to why this relationship exists is that testosterone directly impacts our genetic material in ways that decrease inflammation. Like a key fitting into a keyhole, testosterone binds to androgen receptors, which are located on most cells in the body. That grants testosterone access to DNA within the cell. It locks onto sites on the DNA that are built to interact with the hormone and changes the way the body reads and expresses that genetic code.

Experiments show that when testosterone changes gene expression, it can counter inflammation in the body. Inflammation is a state where the body releases white blood cells and chemicals to fight disease and injury good in the short term, but harmful to the heart when it becomes a chronic state.

If youre experiencing symptoms of low T such as fatigue, erectile dysfunction, low libido, depression, and loss of muscle mass it might be worth getting your levels checked. From there, have a conversation with your doctor about treatment.

But be aware that it may not protect your heart. Testosterone replacement therapy (TRT), in which synthetic testosterone is administered as an injection or topical ointment, can help raise testosterone levels, but there isnt good evidence that it reduces the risk of heart problems, Werstuck says. In fact, some studies suggest it might increase this risk. That doesnt mean you should rule out TRT, but dont spring for it without a conversation with a medical professional.

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The Worrisome Link Between Low Testosterone And Heart Problems - Fatherly

Hey there! If youve ever wondered about the buzz surrounding testosterone boosters, youre not alone. With claims of increased energy, improved muscle mass, and enhanced performance, these supplements have caught the attention of many. Lets delve into what the science has to say about testosterone boosters and get a clear picture of what you can expect.

First things first, lets talk about the research. Numerous studies have explored the effects of testosterone boosters on various aspects of health and performance. Its like diving into a treasure trove of information. Many of these studies indicate that testosterone boosters can indeed have some positive effects, especially in individuals with low testosterone levels.

One area where the research shines is in addressing conditions like hypogonadism, where the body doesnt produce enough testosterone. Testosterone replacement therapy (TRT), a medical intervention involving testosterone boosters, has shown promising results in improving symptoms associated with low testosterone. However, its crucial to note that these studies often involve individuals with diagnosed medical conditions. If youre considering testosterone boosters for general health or performance, its wise to check out the specific details of these studies to understand the context and applicability to your situation.

Now that youve got the scoop on the science, lets dig deeper into what makes up these testosterone boosters. Think of it as a behind-the-scenes tour of the supplement world. Many testosterone boosters boast a blend of ingredients believed to enhance testosterone levels and overall vitality.

One common ingredient youll find is fenugreek, a herb with a long history of traditional use. Studies suggest that fenugreek may have a positive impact on testosterone levels, making it a popular choice in testosterone booster formulations. Another player in the mix is D-aspartic acid, an amino acid that has been linked to increased testosterone production in some studies.

Zinc and vitamin D are often the dynamic duo in testosterone booster ingredients. These essential nutrients play crucial roles in testosterone synthesis, and their inclusion in these supplements aims to support overall hormonal health. Its like having a well-curated playlist each ingredient contributes its unique notes to create a harmonious blend.

Understanding the components of testosterone boosters allows you to make informed choices based on your preferences and potential dietary gaps. If youre curious about the specific benefits and mechanisms of these ingredients, check out reputable sources to unravel the mysteries behind the testosterone booster formula.

As interest in testosterone boosters surges, the market has become a bustling landscape with a plethora of options. Its like stepping into a busy marketplace, each stall vying for your attention. Navigating this market maze requires a keen eye, a dash of skepticism, and a good understanding of your own needs.

One crucial factor to consider is product quality and reputation. Not all testosterone boosters are created equal, and the market is teeming with both effective and questionable options. Checking out customer reviews, testimonials, and expert opinions can guide you through the maze, helping you identify products that have garnered positive feedback and trust within the community.

Price points can vary, and while budget-friendly options exist, its essential to strike a balance between cost and quality. The most expensive option isnt necessarily the best, and vice versa. Take the time to explore different brands, compare ingredients, and check out the overall value each testosterone booster offers.

Keep in mind that what works for one person might not work for another. Personal preferences, dietary restrictions, and individual health conditions should play a role in your decision-making process. As you navigate the market maze of testosterone boosters, arm yourself with knowledge, read reviews, and check out the options that align with your goals and values.

Now, lets switch gears and explore natural avenues for boosting testosterone. Its like taking a scenic route a bit slower, but filled with sustainable and holistic choices. While testosterone boosters are an option, several lifestyle factors can positively influence your hormonal health.

Regular exercise is a powerhouse when it comes to maintaining healthy testosterone levels. Both resistance training and aerobic exercise have been linked to increased testosterone production. Its like giving your body a wake-up call, signaling it to optimize its hormonal balance.

A balanced and nutritious diet is another key player. Nutrients like vitamin D, zinc, and omega-3 fatty acids support testosterone production. Incorporating foods like fatty fish, nuts, seeds, and leafy greens into your diet provides a natural boost to your hormonal health.

Adequate sleep is often underestimated but plays a significant role in overall well-being, including hormonal balance. Its during deep sleep that your body engages in crucial processes, including testosterone synthesis. Prioritizing quality sleep can be a game-changer in supporting your bodys natural vitality.

Reducing stress is a final but vital component. Chronic stress can contribute to hormonal imbalances, affecting testosterone levels. Incorporating stress-reducing activities like meditation, yoga, or even a simple walk into your routine can positively impact your overall health.

While testosterone boosters have their place, exploring these natural ways to boost testosterone provides a holistic approach to supporting your bodys vitality. If you want to adopt a lifestyle that aligns with your hormonal health goals, check out these natural strategies to enhance your overall well-being.

Now, lets tackle the muscle-building myth. Youve probably heard claims that testosterone boosters can transform you into a muscle-bound powerhouse. While there is some truth to this, setting realistic expectations is essential. Testosterone plays a crucial role in muscle development, and studies have suggested that testosterone boosters may contribute to increased muscle mass, particularly in resistance training.

However, its not a magic potion that guarantees Hulk-like gains overnight. Your workout routine, diet, and overall lifestyle play equally vital roles in achieving muscle growth. Think of testosterone boosters as your sidekick in the journey, not the sole hero. If youre curious about the specifics of muscle-related studies, check out the research to understand how testosterone boosters can complement your fitness efforts.

Alright, now for the real talk the risks and rewards. While theres promising research, its crucial to be aware of potential side effects and safety considerations. Some studies suggest that long-term use of testosterone boosters may pose risks, including cardiovascular issues, liver damage, and mood swings. Its like walking a tightrope balance is key.

Before jumping into the world of testosterone boosters, its wise to check out the safety profiles of specific supplements and consult with a healthcare professional. Your unique health conditions, medications, and overall well-being should be considered to determine if testosterone boosters are a safe option for you. Understanding both the rewards and risks is essential in making an informed decision about incorporating these supplements into your routine.

So, heres the lowdown: the science on testosterone boosters is promising, but its not a one-size-fits-all solution. As you navigate the testosterone booster terrain, armed with research insights, it ultimately comes down to what works for you. Consider your health goals, consult with a healthcare professional, and check out reputable sources to make an informed decision.

Remember, your journey is unique, and what matters most is your well-being. Whether you decide to explore testosterone boosters or take a different path, make choices that align with your health priorities and lifestyle. The research is there to guide you, but the final decision is in your capable hands. Cheers to your health journey!

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What Science Says About Testosterone Boosters: Understanding the Research - MWWire

We are not even half a month into the new year and there is, already, some sort of a controversy regarding the results of a world champions drugs test. As fans may have heard by now, one of Artur Beterbievs post-fight drugs tests ahead of tomorrows three-belt defence against Callum Smith in Quebec, came back with elevated levels of HGH (human growth hormone) and testosterone.

Kevin Iole broke this story.

Now, to be clear Beterbiev has NOT failed a drugs test, his results on December 6 had an atypical finding, with elevated levels of both HGH and testosterone. An atypical finding is not the same as an adverse finding and the Smith fight will go ahead. However, quite naturally, Smith and his promoter Eddie Hearn have had something to say about these results. As Smith put it, Beterbiev hasnt failed a drugs test, but he hasnt passed one.

Beterbiev doesnt want to hear any suggestions at all of him having done anything wrong, with the WBC/WBO/IBF light heavyweight champ and his team keen to point out how the fighters three follow-up tests conducted on December 15, December 21, and January 3 all came back negative.

However, Beterbiev has laid into Smith, who he says intends to disseminate misleading information about my VADA testing program for this fight.

Let me be clear now, Beterbiev continued via his official statement, I am a clean athlete. I have never tested positive for a banned substance throughout my amateur and professional career and I complied with all VADA requirements and protocols during the build-up to this fight. Any attempt to imply otherwise, through innuendo or suggestion is slanderous and libellous. This conduct is beyond acceptable trash-talk in combat sports. Callum is already searching for excuses, looking for a way out. See you Saturday.

In the meantime, Hearn says he would like to get more information as to why Beterbievs HGH and testosterone levels were advanced.

(It was) not an adverse finding, an analytical finding, but still raised levels which as a promoter of a fighter in the other corner is a concern, Hearn said to the media as filmed by Fight Hub. So weve been working with VADA to try to understand the reasons why. Contractually we cant do anything about it because it was not an adverse finding but it was an analytical result of blood and urine of raised levels of HGH and testosterone.

So, the fight will go ahead but Hearn will continue to look into the matter. In all likelihood, this will all go away pretty soon. However, any little bit of a controversial element attached to a big-name fighters drugs tests is bound to generate headlines for the time being.

Some critics may well suggest Smith now has a potential gift-wrapped excuse to use if he loses to Beterbiev on Saturday.

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What To Make Of Artur Beterbiev's Elevated Levels Of HGH And Testosterone? - East Side Boxing

Are Testosterone Boosters Any Effective for Muscle Gains and Increasing Testosterone Levels in Men?  EssentiallySports

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Are Testosterone Boosters Any Effective for Muscle Gains and Increasing Testosterone Levels in Men? - EssentiallySports

Low Testosterone: Help is on the Way  Men's Journal

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Low Testosterone: Help is on the Way - Men's Journal

Many products claim to increase your testosterone levels, but not all of them are effective or reliable. TestoFuel Testosterone Booster is one of the best products you can find, because it has a clear and focused formula that works well. You can see this in how the formula uses ingredients that are not only strong by themselves, but also work better together.

For example, lets look at two ingredients: maca root and boron. Both of them are common ingredients, especially boron, but you dont often see them together. This is because they both do the same thing, mainly lowering estrogen that naturally lowers testosterone. The thing is, they both do it in different ways, which are good on their own, but even better when combined. This makes TestoFuel Testosterone Booster a great choice for helping you shape your body, as it replaces estrogen caused fat with testosterone caused muscle.

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This is just one of many reasons why TestoFuel Testosterone Booster has been the best testosterone booster for a long time, its just a great formula that no one can beat.

Lets look at the most important parts of TestoFuel Testosterone Booster, like its formula, benefits, effects, price, and more, to help you decide if this is the right product for you.

TestoFuel Testosterone Booster is a supplement that acts like anabolic hormones in your body in a natural way. It is made with some of the well-known natural ingredients like herbs, extracts, and other vitamins and minerals, all of which have been tested and proven by science. The supplement is mainly for people who want to increase their muscle size and strength as part of their fitness goals. Thats why it is more popular among people who love working out and building muscles.

TestoFuel Testosterone Booster makes your body produce more testosterone naturally, releases it faster, and prevents it from changing by sticking to other things that lower it. This way, it keeps your testosterone level high. It also helps with other health problems that happen when you have low testosterone.

If you take TestoFuel Testosterone Booster regularly, you can get back your energy and mental sharpness that you might have lost because of different reasons like sickness, surgery, ageing, etc.

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TestoFuel Testosterone Booster is a product that follows high standards and is made with a modern formula that uses ingredients that are based on the latest research. Each ingredient in the supplement has its own amazing health benefit. Here is a quick summary of the different ingredients that make TestoFuel Testosterone Booster strong and effective:

D-Aspartic Acid (DAA):

D-Aspartic Acid is one of the strongest ingredients and is found in most supplements that boost testosterone. TestFuel has 2000 mg of it in every serving.

This amino acid changes the hormone that is made by a part of your brain and makes your body have more free testosterone. This also makes your body produce more growth hormone, and taking DAA regularly not only fixes your low testosterone but also makes your muscles grow faster.

Oyster Extract:

A study has shown that oysters have amazing properties that help with various problems in men like not being able to get hard, low desire, low energy, etc. Oysters have a lot of zinc, which is an important nutrient for making more testosterone and keeping your testosterone level high.

Fenugreek:

TestoFuel Testosterone Booster Ingredients Fenugreek

A wonder herb loaded with crucial nutrients like zinc, selenium, and magnesium, fenugreek blocks the hormone-binding globulin which actually tends to reduce the amount of free testosterone in the body creating a deficiency. Fenugreek, thus, increases its bioavailability in the body significantly.

Vitamin D:

Vitamin D is vital for improving immunity, fortifying bones and muscles, and promoting muscle growth. All of these are related to a healthy testosterone level. The improvement in bone and muscle health increases the bodys stamina thus an extended workout time.

Maca:

An age-old herb, Maca is known to improve endurance in fitness enthusiasts, reduce fatigue, and improves concentration. It also improves health in athletes.

Ginseng:

TestoFuel Testosterone Booster Ingredients Ginseng

Ginseng elevates the level of nitric oxide in the blood which helps in increasing muscle mass. It regulates the testosterone level, increases and combats fertility issues, erectile dysfunction, etc.

Boron:

Boron hinders the hormone binding protein and thus increases the level of free testosterone in the blood. It also increases the effectiveness of vitamin D and enhances mood.

Magnesium:

One of the essential nutrients, magnesium supplementation helps increase the metabolic rate which makes way for better absorption of all the other important nutrients in TestoFuel Testosterone Booster. It thus promotes muscle development and increases bone density and strength.

Vitamin B6:

Vitamin B6 intake activates the enzymes in the body which increases blood circulation, improves metabolism, and elevates testosterone production. It also helps rapid recovery post-workout.

Zinc And Vitamin K2:

Both nutrients are important in giving a significant boost to testosterone levels. A deficiency in zinc can cause a rapid decline in testosterone leading to an imbalance.

Many people around the world have given positive feedback on TestoFuel Testosterone Booster, especially those who do sports and bodybuilding. You can see their comments on the official website and on Amazon. These comments show that the product is real and has the benefits that it promises. The people have also shared pictures of how they looked before and after using TestoFuel Testosterone Booster. This shows that they trust TestoFuel Testosterone Booster and are happy with the results.

Also, TestoFuel Testosterone Booster uses only good and tested ingredients. They can make more testosterone in the body and help in building muscles, burning fat, and improving health. The supplement does not have any secret ingredients and is honest about what it contains.

As we said before, every TestoFuel Testosterone Booster serving has 10 high-quality ingredients. These not only make more testosterone in the body but also give many other health benefits that are linked to a good testosterone level. The main benefits are:

More muscle growth Faster fat loss Higher Better metabolism More energy Less tiredness Better mood and performance Quicker recovery after exercise

TestoFuel Testosterone Booster is very safe because it uses only natural ingredients and no chemicals. So, it is good for men of different ages but they must be over 18 years old. It is best for men over 30 who have low testosterone levels because of aging. Also, since TestoFuel Testosterone Booster helps to increase muscle size, men who do hard workouts, bodybuilding, and shaping can get a lot of benefits from this product.

Because of the all-natural ingredients, TestoFuel Testosterone Booster is a safe supplement, not like fake steroid injections. It does not put fake testosterone in the body, but it uses strong and tested ingredients to make the body produce more testosterone naturally. This supplement is much better and safer than hormone replacement therapy or any other artificial way.

But, every persons body is different and reacts differently. So, it is not possible to say that the supplement will not cause any side effects. Some men with sensitive systems may feel some mild effects at first because some ingredients are very strong. But, they may go away soon, once the body gets used to the product.

TestoFuel Testosterone Booster is a supplement that you can take safely because it uses natural and tested ingredients. The brand is honest about its products, and they do not have any hidden substances or chemicals that can harm your health.

But you should know that some of the ingredients have a high dose to make the product work better for the users to get quick results. Some users who have sensitive bodies may feel mild effects like headache, nausea, diarrhoea, or a small change in their health. For example, some people may get slight diarrhoea from D-aspartic acid. And some people who are new to the supplements may get dizzy or headache from fenugreek.

However, there are many good reviews about TestoFuel Testosterone Booster, and no one has reported any serious side effects. When the body gets used to the supplement, the mild effects also stop.

One important thing to say here is that you should check your testosterone level before you start taking this supplement. Testosterone boosters are for those who have low testosterone, and the supplements can hurt you if you already have a normal level. Too much testosterone than what the body needs can cause mood swings, damage the liver, make you gain weight, keep you awake, cause heart problems, and more.

You should take 4 capsules of TestoFuel Testosterone Booster every day. The best time to take them is after each meal or snack, so they are spread out evenly throughout the day for best results. You can drink them with water or any other drink. Staying regular with these supplements, along with a healthy way of living, is also important to get the right results. One bottle of TestoFuel Testosterone Booster has 120 capsules which is enough for one month.

TestoFuel Testosterone Booster gives you many main and extra health benefits that come from having a good testosterone level. But to know better if this product is suitable for you, here is a summary of the good and bad points of the product.

Benefits:

Natural ingredients Safe with no side effects Many health benefits Speeds up muscle growth Great for fitness experts and bodybuilders Quick recovery from muscle or tissue injuries Makes your brain work better Available on different online shopping platforms Worldwide shipping Different ways to pay Made in GMP-approved and FDA-controlled facilities

Drawbacks:

Need to be regular with the dose Supplements work best with a hard workout The risk of forgetting a pill is high as it is 4 pills spread throughout the day Some may find it a bit costly

One bottle, which is one months supply, will cost you $65. You will be able to save more if you buy more. For example, two months capsules will cost $130; with three months of supplies, you get 1 bottle free, and the package costs $195; besides that, they offer free shipping in the UK and US.

You can buy TestoFuel Testosterone Booster from their official website. If you see this product in some other online stores like Amazon etc., there is a high chance that it is from an unapproved dealer and the products quality may be doubtful. That is why, to be safe, it is always suggested to buy from their own website.

TestoFuel Testosterone Booster has many benefits, making it a good option. It does the main function of increasing the testosterone level as well as it says to. The very positive reviews from its users show the quality of the product along with the research-support it has on each of its ingredients.

The good thing is that TestoFuel Testosterone Booster does not trick the customers and keeps full honesty about its aim and ingredients. That being said, this is a food supplement and will only work if you keep a healthy and active lifestyle. This alone cannot solve the testosterone shortage problem and has to be joined by the right kind of food too.

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The Benefits of TestoFuel Testosterone Booster for Muscle Growth and Health - Deccan Herald

Observation of farmed red deer took place in a deer facility belonging to the Institute of Animal Science (V...V.) at Podlesek, Praha, Czech Republic (500302.2"N 143537.1"E).

Setting up a classical control is a problem in a study like this. Without it, we could not fully distinguish whether the social environment causes differences in hormone levels and antler growth or whether specific individuals (with particular hormonal levels and antler growth characteristics) are more or less likely to aggregate with others. Without a full control, it is not possible to discount the hypothesis that internal characteristics of individual males could influence our results. We have previously shown that antler size has high repeatability in subsequent seasons during ontogeny56. Moreover, even though the males had shown behavioural plasticity, their individual attitude to seeking or avoiding interaction had been maintained despite the modifications of the social environment49.

In addition to our main experimental season (Season 1), we also had data on hormones and antler sizes from the following two seasons (Season 2 and Season 3). We, therefore, presumed that if the cause of the results were based on characteristics which were individual-specific, then the hormonal and antler values recorded for individual males in this study in Season 1 should correlate with those of the same individuals in the following season or seasons. On the other hand, if the hormonal and antler characteristics displayed by individual males in Season 1 were primarily a consequence of the males social tactics, the repeatability of hormonal and antler values between Season 1 and Season 2 should be lower than that between Season 2 and Season 3, when the males lived in the same environmental conditions.

Seventeen semi-tame red deer males (one male aged 9, seven aged 6, six aged 3, and three aged 2) belonging to the same bachelor group since birth were available at the beginning of the observation at the facility, within an area of approximately 4ha. This area was divided into six enclosures. Each enclosure (about 0.7ha large) contained a shelter (a wooden, roofed barn with one side permanently open with the entrance of approximately 24 m2), a water reservoir, and a mud pool for wallowing. During the main observation period (from 17th April to 28th August in Season 1, the period of antler growth), all enclosures were interconnected by two (in the first and last enclosures) or three permanently opened gates in other enclosures allowing the deer to move around and aggregate with or separate from others. In contrast, for control purposes, in Seasons 2 and 3, the same males were kept in three interconnected enclosures, each 0. 7ha in size, i. e. their living space in Seasons 2 and 3 represented about 50% of the area in Season 1. The animals fed predominantly on the natural pasture of the enclosures and were supplemented with hay (ad libitum) and occasionally also with potatoes, beets, apples, pears, barley and oats. The animals were identified with coloured, numbered collars and in Season 1 equipped also with GPS collars (Lotek Wireless Inc. GPS_3300, position readings with an error of less than 5m). When this study ceased, all animals stayed at the facility for future investigations.

According to European and Czech laws, the experimental deer facility is an accredited research centre for the ethical use of animals in research (60444/2011- MZE-17214). The experimental proposal no. MZe 1297 was approved by the Animal Care and Use Committee at the Ministry of Agriculture of the Czech Republic. We confirm that all methods were carried out following relevant guidelines and regulations and are reported in accordance with ARRIVE guidelines.

In Season 1, observations were designed to record agonistic interactions between animals when competing for supplemental food. At the time of observation, deer were fed a mixture of soya, barley, oats and a mineral/vitamin premix, which amounted to an average of 0.7kg/day/animal. When the supplemental food was presented, it usually attracted all males regardless of whether they were otherwise in groups or associated individually in the paddocks. Thus, at the time of provision of the supplementary food, all the males met together even if otherwise they preferred to avoid encounters with other individuals.

The food was carried to the observation place in a wheelbarrow and presented in several piles to encourage mild competition over a scarce resource (serious competition was prevented to preserve good welfare of the stags). The food piles were tipped from the wheelbarrow in 8 or 9 piles about 2m apart, in order to encourage competition without exacerbating it. This method has already been proven valid in previous studies e. g.,15,49, etc. Each observation session took place in the morning (between 9.00 a.m. and 11.30 a.m.) and ranged from 20 to 60min (depending how long the deer stayed at the site of supplementary feeding). In Seasons 1, 2, and 3, observations took place from 1 to 5 times per week between 1st May and 28th August (with an average equal to 3). In total, the deer interactions were observed for 37h in Season 1, 30h in Season 2, and 15h in Season 3. All deer were semi-tame and started to compete over the food as soon as it had been presented, running from one pile to another trying to eat as much as possible. When a feeding deer was challenged by others, it either escaped to another pile or defended itself. All the observations were made into a voice recorder and then transcribed into a table using Microsoft Excel. We recorded any occurrence of an approach of one male to another, any attack, threat gesture, or fighting, which caused an apparent displacement of the approached individual49,59. As in previous studies reviewed in55, we determined dominance status for each pair of males on the basis of the agonistic interactions observed. We regarded as dominant the males who won more agonistic encounters than they lost in any dyad, as subordinate the ones who lost more often than they won within the dyad, and as indifferent the males in a dyad with no agonistic interactions.

GPS collars measured inter-individual distances between males in Season 1 only. Positions were programmed to be recorded once per hour. This enabled us to obtain records of inter-individual distances during the observation period with an average of 90.404.6m (meanSE) per dyad (n=272) over the observation period, producing a reliable picture of mean inter-individual spaces whole period. In Seasons 2 and 3, we did not use GPS collars and made no detailed spatial observations as done in Season 1.

In all three study years, we weighed the males once a month (5 times between April and August), collected blood samples for the hormone analysis in a physical restraining facility (crush). All deer involved were used to this procedure and had undergone it since birth. No chemical restraint was used besides physical restraint. In Season 1, when collecting blood samples, we downloaded GPS records from data loggers. In all seasons, we measured the antlers after casting, as previously described e. g.,60 and used the total antler length, the final sum of the length of all tines, points and beams divided by 261, as a dependent variable.

Analyses of T and C concentrations were performed in the laboratories of ELISA development, s.r.o. (Velk ernoseky, the Czech Republic). T concentration was measured by RIA Kit from Beckam Coulter (code IM1087). T antibody for this RIA Kit is species-nonspecific. The radioimmunoassay of T is a competitive assay. Before the assay, plasma samples were extracted with ethyl ether; the solvent was evaporated, and the dry residues were re-dissolved in the recovery buffer of the kit. The re-dissolved extracts and calibrators were then incubated with 125I-labeled T, as a tracer, in an antibody-coated tube. The concentration range was up to 23ng/mL, the assay's detection limit was 0.1ng/mL, intra-assay-precision was 8.6%, and inter-assay was 11.9%. The recovery of the extraction step was 90%.

C concentration was determined by RIA Kit from Beckman Coulter (code IM1841) previously validated only in cattle62,63. C antibody for this RIA Kit is also species-nonspecific. The radioimmunoassay of C is a competitive assay. Samples and calibrators were incubated in monoclonal antibody-coated tubes with 125I-labeled cortisol tracer. The concentration range was up to 2000nM, the assay's detection limit was 5nM, intra-assay-precision was 9.4%, and inter-assay was 12.6%.

All data were analysed with the aid of the SAS System (SAS, version 9.4).

Previous studies have shown that it is essential in assessing relationships between social behaviour and physiology to record and analyse measured characteristics in as much detail as possible e. g.,6. Therefore, we preferred to analyse the inter-individual pairwise relationships rather than rely upon any form of summarized values.

(i) In the main observation period (Season 1), for each male, we collected for each observation the inter-individual mean distance (meters) from each of the herd mates (i.e., 16 inter-individual distances per male). A cluster analysis (PROC CLUSTER, with TYPE=NOMINAL and METHOD=HIERARCHICAL) was used to divide the mean inter-individual distances resulting into two groups, Associates (males keeping together) and Distant (those living apart). According to their involvement in interactions during the feeding competition, these latter (distant) dyads were further subdivided as Indifferent (i.e., no interaction within the dyad was recorded), or Non-associates (i. e., dyads keeping mutual distance, interacting during the feeding competition only). In conclusion, three levels of mutual relationship between the individual stags were considered: Associates (keeping together), Non-associates (keeping distance but interacting when meeting during the feeding) and Indifferent (keeping distance, non-interacting). For each male, we then calculated the "Proportion of Associates" of all dyadic relationships (% of individuals from all 16 possible dyadic groups who were identified as Associates of the focal individual) and the Proportion of Non-Associates relationships (% of individuals identified as Non-Associates within any dyadic group). At this point, however, it should be pointed out that the classification of Associates, Non-Associates and Indifferent concerns dyadic distances, not the categorization of males. Thus, each individual could be Associate with one male, Non-Associate with another male, and Indifferent with other males. It, therefore, depended on whom the focal individual had interactions with, and which conspecifics preferred more than others.

For each subject we had available also other characteristics of interactions (listed in Table 2), between him and all other males such as the number of attacks, wins, losses, etc. For the analysis, we used the mean values of all quantifiable variables over the whole period for each subject and all its dyads. Having 17 males with 16 relationships each, we obtained 272 dyadic records in total.

To check for possible multicollinearity, we first calculated correlations (PROC CORR) between the individual metrics involved (Table 2). Significant correlation was found between the Bodyweight at the beginning of the observation and at the end of the entire experimental period (MayAugust; r=0.91, P<0.0001), between Bodyweight and Weight gain (r=0.83, P<0.0001), between Age and Bodyweight (at the beginning of the observation r=0.84, P<0.0001; and at the end of the observation r=0.71, P<0.0001. We subsequently made a judgment of the extent of collinearity by checking related statistics, such as Tolerance value, Variance Inflation Factor (VIF), Eigenvalue, and Condition Number and using TOL, VIF and COLLIN options of the MODEL statement in the SAS REG procedure. We discovered apparent collinearity between all variables characterizing agonistic interactions (i. e., Sum of all agonistic interactions of any given type, Wins, Losses, and Number of attacked conspecifics). When either of these characteristics entered the REG procedure alone, the lowest tolerance value did not drop below 0.13. The highest variance inflation value did not exceed the value of 7.5. Also, there was no case of small eigenvalues combined with the large corresponding condition number. So, there was no threat of other multicollinearity indicated by these results.

Across the models, where appropriate, count variables were log-transformed (natural logarithm transformation) to improve the normality of residuals and to reduce skewness.

Since the issues analysed in this study represent more complex causality, we used the information-theoretic approach (IT-AIC) for estimating the effects of the factors on dependent variables64.

Associations were subsequently sought between C concentrations (ii), T concentrations (iii), or total antler length as dependent variables and the remaining fixed factors (Table 2) using a multivariate General Linear Mixed Model (GLMM, PROC MIXED). To account for the repeated measures on the same individuals, all analyses were performed using PROC MIXED with ID of the individual male as a random effect. For each dependent variable, we constructed a set of multiple a priori hypotheses and added a Null model. Where appropriate, we included interaction terms. Specifically, for log-transformed C concentrations, we set up 38 alternative hypotheses, for log-transformed T concentrations 26 hypotheses, and for Total antler length 90 hypotheses (Supplementary Table S4). For each dependent variable (i.e., C, T, and total antler length) we generated all GLMMs in the Supplementary Table S4 and converted values of fit statistics.

Since the introduction of Akaike's Information Criterion (AIC), more information criteria have been developed with differing mathematical properties and philosophies of model selection65. We used expanded information criteria AIC, AICC, BIC, CAIC, and HQIC to select a true model, as recommended by Christensen65. Then we compared the candidate models by ranking them based on the information criteria being used (PROC RANK). The model with the lowest value (i. e. closest to zero) is considered to be the "best" model64,65. To see if the best model has merit, we compared our model to the null model for all dependent variables and all fitting criteria, showing delta (null best model) and a relative information loss [exp((nullbest)/2)], an approach adapted from Burnham and Anderson64.

The differences (i) between the Fit statistic values (the smallest values indicating the best fitting model) were sorted according to AIC values. Akaike weight wi can be interpreted as the probability that Mi is the best model (in the AIC sense, that it minimizes the KullbackLeibler discrepancy), given the data and the set of candidate models e. g.,64. For five models with the lowest AIC values, we therefore calculated AIC, Akaike weights wi, and for estimating the strength of evidence in favour of one model over the other we divided their Akaike weights wmin/wj (AIC Odds)64.

Associations between the dependent variable and countable fixed effects are presented by fitting a random coefficient model using GLMM as described by Tao et al.66. We calculated predicted values of the dependent variable and plotted them against the fixed effects with predicted regression lines.

Several statistical methods are typically used to show comparability or repeatability67. As previously49, we chose Lins concordance correlation coefficient68 using the SAS macro described by67 and Kendalls tau-b correlation coefficient to estimate a measure of association of the hormonal and antler measures of the same subjects between Season 1 Season 2, and between Season 2 Season 3. For computing Kendalls correlation coefficients and its confidence interval estimation, we applied macro by Looney69. From the Seasons 1 to 3, males group consisted of the same individuals. Decreasing N on comparisons between seasons (Table 4) reflected that some males were removed from the facility for other purposes (four in Season 2 and one in Season 3).

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