Testosterone Pills: How Oral TRT Solutions are Changing Testosterone Therapy

Comparing Kyzatrex and Jatenzo: Oral Testosterone Therapies for Men on TRT

 

FDA Approved Oral Testosterone for Men on TRT

For men with low testosterone, TRT has become a therapeutic option which has positively changed, countless lives for the better. TRT as a medical treatment has been dominated by injectable testosterone like cypionate and enanthate, topical creams and gels, which are absorbed through the skin like Andro gel or even patches and pellets that get inserted into the skin.  These are not always the preferred choice in terms of patient’s preference so fortunately, now there is a more convenient alternative in oral testosterone pills that have been developed an FDA approved. Two popular options are Kyzantrex and Jatenzo which are both oral testosterone replacement therapies that have FDA approval. Each has unique characteristic which separate them from one another.  

Here we discuss and compare the two of them showing how they work, what their benefits are and why men with low testosterone may prefer oral pills over the more traditional injections, creams, etc. 

 

FDA Approved Oral Testosterone 

So in terms of the development of these medications, both Kyzatrex and Jatenzo are oral testosterone replacement therapies which received their FDA approval for treating adult men with hypogonadism. Jatenzo was the first of its kind, which got approved by the FDA in March of 2019, which was a huge leap forward in HRT as it offered a non-invasive, convenient alternative to injections, pellets, patches and gels. Marius Pharmaceuticals, who manufactures Kyzatrex, followed shortly after, receiving their FDA approval in August 2022. Kyzatrex is seen as a better version of Jatenzo by many with its formulation designed to optimize absorption and provide consistent testosterone levels. Both medications approval by the FDA were based on clinical trials which demonstrated their effectiveness in restoring testosterone levels to normal physiological ranges, while maintaining what is considered to be an acceptable safety profile.

 

The reason these oral testosterone medications are considered important developments in TRT is because of the dangers associated with oral testosterone in the past. Before the development of medications like Kyzatrex and Jatenzo, oral TRT was largely avoided by all reputable medical professionals because of the serious risks associated with older formulations. Traditional oral testosterone pills/capsules and tablets, such as methyltestosterone, was processed through the patients liver (first-pass metabolism), which led to hepatotoxicity — causing liver strain and, in some cases, serious liver damage. This included major medical conditions such as liver tumors and cholestasis (impaired bile flow). These very serious liver-related risks made oral testosterone a less viable option due to the high probability of complications and side effects, so most physicians wisely preferred prescribing injections or transdermal systems like gels to their patients. The more recently developed oral testosterone medications were specifically designed to bypass the liver and be absorbed through the lymphatic system, which significantly reduces the risk of liver toxicity and thus makes oral TRT a much safer option today and one that physicians can now offer their patients.

 

How do testosterone pills work? 

 

Kyzantrax and Jatenzo were both developed to increase testosterone levels back to acceptable therapeutic ranges for men that have hypogonadism. Hypergonadism is a condition where the man’s body is no longer producing enough testosterone and can occur for multiple reasons so it’s important to get properly evaluated and diagnosed by your physician before jumping to conclusions and trying therapies without proper medical guidance. 

Both of these oral medication‘s are taking orally. However, the mechanism of actions and formulations have important distinctions, which a physician and patient need to discuss and consider before being prescribed. 

 

For example, Jatenzo is a form of oral testosterone undecanoate capsule.   Testosterone undecanoate is at its core, a long chain ester of testosterone which gets absorbed in the body, primarily via the lymphatic system, as opposed to the liver, which helps it to reduce what’s known as first pass, hepatic metabolism.   This has been a challenge in the past with testosterone often causing patients who would take oral testosterone to have liver complications, but this new medication seems to have solved that problem. It’s taken twice a day with food, preferably meals that have fat to help in its lymphatic absorption. Once ingested, the ester bond is broken, releasing active testosterone into circulation within the bloodstream.

 

Kyzatrex however, is also an oral testosterone undecanoate, but comes in a soft gel formulation unlike Jatenzo. Kyzatex uses what’s called a self-emulsifying drug delivery system, which helps to increase the absorption rate through the lymphatic system similar to Jatenzo. It too is taken twice daily with food. The soft gel capsules are designed so that they can easily and quickly dissolve, and its formulation helps to improve what’s known as bioavailability, which make sure there’s a more consistent rate of testosterone absorption in the body.

 

Both of these medications rely on food intake to help maximize the absorption of the medication which makes adherence to the prescribing and dosing guidelines important because without dietary fat, the bioavailability of both of these medications can decrease significantly. Even though both of these medication’s are extremely similar and have similar mechanisms of action, Kyzatrex is widely believed to have a formulation which promotes a smoother pharmacokinetic profile which may potentially result in a steadier hormone balance and testosterone levels throughout the day.   

 

What are the benefits of oral testosterone?

The development of oral TRT pills like Kyzatrex and Jatenzo help address several common issues that many patients have with traditional TRT medication’s.  

More convenient and easier to use   

One of the services that we offer our patients is education and assistance, and administering injectable testosterone, such as testosterone cypionate or enanthate. Most patients that we have are unfamiliar with how to self-administer an injection so they need to be shown the proper way to handle the medication and give themselves an injection. However, this is not an issue and is one of the most obvious advantages of oral TRT in the form of how convenient it is. Most men already know how to swallow a pill, especially those that are hesitant to inject themselves or don’t want the hassle of having to visit a clinic weekly for their testosterone injection. These patients truly appreciate how simple taking a pill is.  Transdermal testosterone gels are also convenient and non-invasive. However, many patients complain about how messy they are and are nervous about potentially transferring the medication to another individual or pet for example through skin to skin contact. Patches are also convenient but have been known to cause skin irritations when being worn all day and depending on the situation are clearly visible.  Capsules are more portable and for those men who travel frequently, oral TRT pills. Eliminate the need for refrigerating medication like HCG or having to worry about carrying a syringe in your luggage. Swallowing a capsule in contrast, is a very simple convenient way to start TRT without the risks, hassles or fear involved with other delivery methods. 

 

Consistently steady testosterone and hormone levels

Both Kyzatrex and Jatenzo help to deliver stable levels of testosterone throughout the course of the day, which is beneficial in helping to eliminate the peaks and rows of hormones, which can sometimes be associated with traditional injection TRT meds. Injections like testosterone cypionate or enanthate which have a long acting release of testosterone compared to the oral pills/capsules have a half-life of about a week, which is why they need to be injected at least one time a week. After injecting, testosterone levels will increase significantly and over the course of the seven days, decline, leaving what are known as peaks and troughs.  If not adjusted, some patients may even experience mood swings, irritability, or have difficulty controlling and maintaining their symptoms or even side effects, whereas oral formulations when taken consistently with food, provide an extremely predictable pharmacokinetic profile.  Kyzatrex claims to have an advanced delivery system and may have an edge in this area, providing smoother more balanced testosterone levels that can potentially help to mitigate mood variability and help to sustain energy and reduce fatigue throughout the day when taken consistently.   

 

Reduce the risk of any potential injection related problems

For some patients, the idea of injecting causes fear and even terror because of the discomfort of needles. It’s a major barrier for some men in starting or even maintaining TRT. Known as trypanophobia, the fear of needles can trigger intense psychological distress, including anxiety, panic attacks, and feelings of helplessness. This fear can activate the body’s stress response, which can lead to physical manifestations such as sweating, rapid heartbeat, dizziness, nausea, or even fainting (vasovagal response). For some patients on TRT, just the anticipation of having g to give ones self an injection is enough to cause severe emotional discomfort, reinforcing avoidance behaviors and increasing anxiety around medical treatments. These patients will often stop taking medication without alerting their physician and experience all of the signs and symptoms of low tea when in reality there are other delivery methods that would have been more appropriate for them and beneficial and helping to treat their andropause.

Another issue with injectable testosterone is potentially an increase in red blood cells known as erythrocytosis.   That’s not to say that oral testosterone medication doesn’t have this risk, but it’s believed that a more consistent hormone level in the bloodstream will mitigate the spikes of red blood cell production often associated with injections.

 

So why would someone choose one over the other? Is Kyzatrex orJatenzo better?

Picking the medication that’s right for you can be tricky and choosing between Kyzatrex or Jatenzo is usually a personal choice based on medical history, physician, guidance, and tolerability however, there may be several factors which can influence the patient’s decision.  

One such factor could be the tolerability and side effect profile for the patient.  For the same reason that someone might prefer Tylenol over Advil or Motrin or Excedrin, someone may prefer the way they feel on one of the oral TRT medications over the other.   

Where both of these medications share very similar potential side effects such as increased red blood cell count possible elevation in blood pressure and potential effects on cholesterol levels, some patients have reported better tolerability with one over the other. Clinical trials have shown us that both of these medication’s will effectively raise testosterone levels into normal ranges however, these subtle differences and how they are absorbed and a patient individual Ability to absorb and their metabolism may influence side effects that one patient experiences compared to the next.  

Also, some men feel that kyzatex provides a more balanced smoother, hormonal experience that they felt fewer mood fluctuations, and that could potentially be due to the way it’s absorbed in the body and other patients have said Jatenzo was equally effective and more well tolerated for them, especially if they had been on it for a longer period of time and their bodies had adjusted well to taking it.  

A physician who is experienced with hormone replacement therapy in particular TRT and these oral medication’s may be able to offer guidance based on their patients preferences and results, which once again reiterate the importance of going to an experienced healthcare provider for any medical advice/treatment.  

Ultimately both Kyzatrex and Jatenzo are incredible advancements and testosterone replacement therapy, which are now able to offer more men and effective needle free option to help balance their hormones, improve their overall health and quality of life. They both share similarities and how they work, function, and how they are administrated, however Kyzatrex’s delivery system seems to give it the slight edge in how it’s absorbed and how it’s able to consistently provide testosterone delivery for some patients. The choice between which one to take will come down, ultimately, to the individuals preference and tolerability.  If you take one of these medication’s, and notice some side effects, your physician may recommend switching to determine if the other medication is better suited for you. For many patients, the benefit of oral testosterone and its major appeal lies within its convenience, ability to maintain discretion and the avoiding injections or gels, which are both effective yet not without their own set of complications. As oral testosterone therapy medication’s continue to advance and evolve, these are now becoming a more popular option, which can empower men to treat their low t with greater convenience and confidence.   

www.NovaGenix.org  (561) 277-8260

Hormone Replacement Therapy & Progesterone: Why It Matters for Women's Health

Understanding the Role of Progesterone in Hormone Replacement Therapy (HRT) for Women: Levels, Roles, and Concerns for Women in Menopause

Hormone Replacement Therapy (HRT) has become a vital tool for women that are trying to manage the unwanted symptoms of menopause and improving their quality of life during what can be difficult period for many. There are several hormones at play in women and all have unique functions in the female body. These hormones are constantly fluctuating and when a woman hits perimenopause, they go haywire with some increasing, some decreasing and others becoming erratic. The major hormones that drive a women’s mental and physical health are Estrogen, progesterone, prolactin, hCG, FSH, LH, T3/T4 and testosterone. When that balance is upset, the side effects can be tough to handle.  Hot Flashes, Night Sweats, Mood Changes, Vaginal Dryness and Sleep Disturbances are some of the common side effects that women seek help with from doctors such as OBGYNs, endocrinologists and hormone replacement therapy specialists.

Among the key hormones involved in women’s health, progesterone is one that plays a crucial role, often alongside of estrogen. Understanding what optimal progesterone levels are, its physiological functions in the woman’s body, and the potential health consequences of imbalances are essential for an effective hormone therapy protocol and treatment. In this article, we’ll talk about the role of progesterone in HRT, focusing on optimal levels, its roles in women’s health, the impact of low levels, and the changes observed during menopause.  

How Progesterone Supports Women’s Health Across All Stages of Life

Progesterone, is considered a steroid hormone and is primarily produced by women in the ovaries by the corpus luteum after ovulation. Its primary job is to prepare the uterus for pregnancy by thickening the endometrial lining. It’s important for supporting pregnancy, which is why women undergoing IVF, for example, take progesterone to help prepare their body for implantation and to support the growing fetus. Beyond reproduction, progesterone exerts a significant influence on several different physiological processes.  

• Endometrial Regulation: Probably the most recognized role of progesterone is its interaction with the endometrium. The endometrium is the inner lining of the uterus that plays an important role in the menstrual cycle, pregnancy, and overall reproductive health for women. It counteracts the proliferative effects of estrogen, preventing excessive endometrial growth and helps to reduce the risk of hyperplasia and cancer. This is particularly important in HRT, where estrogen is often prescribed and taken by patients.  
• Neuroprotective Effects: Progesterone has been shown to have calming and has been known to help reduce anxiety (anxiolytic effects). It can also help contribute to mood regulation and may help to improve sleep quality, all side effects that many women experience in perimenopause and menopause. Progesterone is interesting in the fact that it interacts with GABA receptors in the brain. GABA receptors have several important roles such as they help Promote Relaxation & Reduce Anxiety by helping dampen excitatory signals, which reduces stress and anxiety levels. They also help to Regulate Sleep through the inhibiting of overactive neurons, which may contribute to better sleep quality and can even help initiate sleep for those that have a tough time falling asleep at night. They also Control Muscle Tone as GABA activity in the motor system helps prevent things like muscle spasms and tremors. Another important role is that GABA receptors help Modulate Mood & Emotion which can fluctuate significantly in women when their hormone levels are constantly changing.  This is one of the hardest symptoms to deal with as it often affects more than just the woman, but their families, friends and coworkers as well.  
• Bone Health: Progesterone also stimulates cells that help build bones called osteoblasts.  These are essential for bone formation, stimulating new bone growth as well as helping counteract bone loss that naturally occurs with aging, especially after menopause.  
• Cardiovascular Effects: While the effects of progesterone on CV health is complex and still being researched, studies have shown that progesterone may have some beneficial effects on cardiovascular health, including vasodilation as well as having potentially positive impacts on cholesterol and lipid profiles.

Progesterone Levels in HRT: Defining what “Good” levels are.

The million-dollar question is “what’s a good progesterone level for a woman?”   Trying to find out what the "ideal" progesterone level for a woman on HRT is not as simple as it might seems or people would like. It’s not a “one size fits all” approach. Unlike estrogen, where specific target ranges are often established, progesterone levels in HRT are more focused on the individual patient and are context dependent.  What’s considered a "good" level will vary and depend on factors like the type of HRT, the route of administration (oral, transdermal, vaginal), and the patient’s symptoms and risk factors.

Women are all unique and have different baseline progesterone levels. Factors like their age, menopausal status, and overall health will contribute to their specific needs. Some patients might need a higher dose for endometrial protection, while others may require lower doses in order to avoid side effects.   Sequential vs. Continuous is another factor. In sequential HRT, progesterone is administered for a specific period each month, whis is done to try and mimic the natural menstrual cycle of the woman, where in continuous combined HRT, progesterone is given daily alongside estrogen typically to help alleviate unwanted symptoms. The target progesterone levels for these patients will differ between these regimens.   

Also, different forms of progesterone affect absorption so the dose will depend on what type of medication the patient is taking and even what symptom they’re trying to deal with. Oral Progesterone (e.g., micronized progesterone) has what’s called a systemic effect and is often prescribed by physicians for sleep and anxiety benefits.  For many women HRT patients, a focus on endometrial protection is often the primary goal of taking progesterone. Thats why a doctor’s goal is normally to protect the endometrium from estrogen-induced hyperplasia, therefore, the level prescribed should be sufficient to achieve this protective effect and often require Micronized Progesterone (Prometrium).  It’s most recommended for endometrial protection due to it being bioidentical (structurally identical to the body’s own progesterone and well-tolerated with fewer side effects. The pros are it protects the endometrium effectively and supports sleep and anxiety relief (due to GABA receptor effects) as well as been shown to help lower risk of blood clots compared to synthetic progestins. Some of the Cons is that it may cause drowsiness (which is why its best taken at night) and some women have reported experiencing bloating or dizziness. When prescribed the typical dosage is usually 100–200 mg orally at bedtime, but this will be determined for each patient by their prescribing physician.

Topical or Transdermal Progesterone (creams, gels) on the other hand may have variable absorption rates and may not provide adequate endometrial protection. For others on IVF or fertility treatments, Vaginal Progesterone (suppositories) is directly absorbed by the uterus and is commonly prescribed.

How are Progesterone levels tested?

The question to determine the best way to check hormone levels will be patient specific. The 2 options are serum vs. salivary Levels.  Blood Test (Serum Progesterone Test) is the most common method. Progesterone levels measured through a blood test, can help a healthcare provider assess ovulation, fertility, pregnancy health, and hormone balance.  They are usually taken…

• Mid-Luteal Phase (Days 21-23 of a 28-day cycle) – To confirm ovulation.
• During Early Pregnancy – To assess if a woman’s progesterone levels are sufficient to support her during pregnancy.
• When on HRT – To monitor the effectiveness of medication and progesterone balance in hormone therapy.

Serum levels are more commonly used in clinical practice. Low levels may indicate anovulation, luteal phase defects, or hormonal imbalances where high levels may occur during pregnancy, with ovarian cysts, or with excessive progesterone supplementation.  Blood tests are considered the gold standard for assessing progesterone levels in most medical settings. Saliva or urine tests may provide insights but are generally not as reliable for diagnosing hormone imbalances or guiding HRT adjustments and often are not considered a reliable method for clinical testing due to possibly being unreliable.

While specific target ranges vary, the goal is to ensure that progesterone levels are adequate to prevent endometrial hyperplasia for women on HRT. For most patients on cyclical HRT, a mid-luteal phase serum progesterone level is aimed for, where lower levels are acceptable for those who are on a continuous combined HRT. HRT must be an individualized approach. Ultimately, the optimal progesterone level must be determined by a healthcare provider based on individual patient needs and careful monitoring.

Consequences of Low Progesterone Levels

Low progesterone levels, especially in the context of HRT, can potentially lead to several adverse side effects including but not limited to some of the following:  

• Endometrial Hyperplasia: The most significant risk of Low Progesterone for women is endometrial hyperplasia. This condition is characterized by an abnormal thickening of the uterine lining, which can progress to endometrial cancer if not monitored and treated.
• Breakthrough Bleeding: Low progesterone can lead to irregular or heavy menstrual bleeding, especially in sequential HRT.  
• Mood Disturbances: With low levels, progesterone's calming effect can be diminished, which can lead to increased anxiety, irritability, and mood swings.  
• Sleep Disruption: Low progesterone can contribute to a patient suffering from insomnia and poor sleep quality which can then exacerbate hormonal fluctuations.  

Progesterone and Menopause

For women, perimenopause and menopause can be a difficult period of adjustment to how the body acts and responds. During this time, the ovaries gradually begin to cease production of both estrogen and progesterone. This decline in these 2 hormones can lead to a range of both symptoms and physiological changes.  Typically, we see the following in women undergoing menopause.

• Declines in Progesterone Levels: Progesterone production drops significantly during perimenopause and reaches very low levels after menopause. This is due to the ovarian follicles ceasing to ovulate which is when progesterone is mainly synthesized by the woman’s body.  
• Impact on Endometrium: This rapid decline in progesterone generally leads to a thinning of the endometrial lining in the uterus.  
• Symptom Contribution: This combination of both estrogen and progesterone levels being lowered may produce several common symptoms during menopause, like hot flashes, night sweats, mood swings and vaginal dryness.
• HRT's Role: The goal of starting HRT for women struggling with menopause and hormonal imbalances is to replace the declining hormones and elevating them to more suitable levels, alleviating these unwanted symptoms and hopefully improving the patient’s quality of life. Progesterone can play a critical role in HRT, particularly for women with a uterus, to counteract the effects of estrogen and prevent endometrial hyperplasia.  

Optimizing Progesterone Levels on HRT

Since everyone is different, there may be a period of adjustments that have to take place. Effective HRT management requires a collaborative approach between the patient and healthcare provider, and this means scheduling follow up bloodwork to assess the effectiveness of treatments on hormone levels and assessment of symptom resolution.  A wise approach to hormone replacement therapy for women, is to ensure that there is regular monitoring of hormone levels and endometrial health, which we know is crucial to ensuring “good” progesterone levels and to help prevent complications from arising. Individualized Dosing for patients is important as HRT regimens must be tailored to meet the patients’ individual needs and take risk factors into consideration before coming up with ta protocol and dispensing medication to the patient. Open communication with your doctor about symptoms, concerns, and potential side effects is essential and with a good approach and healthcare team behind the patient, it helps to ensure both efficacy and safety of the HRT protocol.

 

All in all, progesterone is a vital hormone in HRT, playing a critical role in endometrial protection and overall well-being for women. Understanding its functions, optimal levels, and the consequences of imbalances is essential for effective HRT management. By working closely with healthcare providers and adopting a holistic approach and maintaining healthy lifestyle habits, including having a balanced diet, engaging in regular exercise, and practicing stress management techniques, can help support overall hormonal balance.   With an intelligent approach, women can navigate menopause with greater confidence and improve their quality of life.  

TRT and Blood Pressure: Does Testosterone Raise or Lower Hypertension Risk?

The Effects of Testosterone on Blood Pressure in Hypogonadal Men

The Complex Relationship Between Testosterone and Blood Pressure in Hypogonadal Men

As more and more men are looking to turn back the clock by starting hormone replacement therapy regimens, there are some concerns regarding the safety and potential for negative side effects from taking medications to influence hormones, specifically testosterone and estrogen in hypogonadal men. Testosterone replacement therapy (TRT) has been widely studied for its benefits in men with low T, or hypogonadism which is a condition characterized by low testosterone levels. The range may vary based on age and other factors; however the typical standard has been between 250-1000 ng/dl. While TRT has been shown to improve several different aspects of health, including muscle mass, strength, libido, bone density, and mood, its effects on blood pressure (BP) still remains a subject of debate amongst those in the medical profession. Patients often ask us if “taking testosterone will increase their blood pressure?” Some studies have suggested that TRT may contribute to hypertension, while others indicate a potential for BP reduction. With conflicting evidence, we have to ask what’s the evidence and why is there a discrepancy between conclusions?  In the following blog post, we’ll investigate the findings from multiple studies to provide a comprehensive overview of the relationship between testosterone and blood pressure in hypogonadal men and how TRT can either contribute to the increase or decrease in BP for patients.

Testosterone and Blood Pressure: Conflicting Perspectives

The effects of TRT on BP have been examined in multiple studies from various researches with differing conclusions. Some reports, such as those from Geoffrey Hackett et al., suggest to us that testosterone undecanoate (TU) therapy may be associated with significant reductions in both systolic and diastolic blood pressure as well as pulse pressure in hypogonadal men, regardless of whether or not they are on any antihypertensive therapy.  Antihypertensive therapy can include medications like diuretics, (ACE) Inhibitors, Angiotensin II Receptor Blockers or beta blockers. In their study, the findings indicate that men who were never on antihypertensive medications experienced BP reductions of -12.5 mmHg (systolic), -8.0 mmHg (diastolic), and -6.0 mmHg (pulse pressure) at final assessment. In contrast, their study showed that the men who did not receive TU showed increases in blood pressure over time.

However, a randomized controlled trial performed by Olesen et al. presented a completely different perspective from Hackett. This study found that men with opioid-induced androgen deficiency who received TRT experienced an average systolic BP increase of 6.2 mmHg, compared to a 7.0 mmHg decrease in the placebo group. Notably, men with higher hematocrit levels and elevated body mass index (BMI) appeared more susceptible to BP increases. These findings suggest that hematocrit levels may modulate BP responses to TRT but it also needs to be stated that these patients all had low T that was a result of taking opioids and not reflective of most typical cases of androgen deficiency.  It’s also important to ask what were the patients testosterone levels PRIO to their opioid dependency? Did they take a Low T test prior or is the reading of low testosterone post dependency the first time their hormone levels were checked? We do know that that heroin and opioids will lower testosterone levels however having a baseline reading that can be validated both before and after is important for researchers to determine valid conclusions and a credible hypothesis.

Hematocrit and Its Role in BP Regulation

One of the primary concerns with TRT is its potential to elevate hematocrit, which can increase blood viscosity and raise BP.  Testosterone therapy has been known to cause secondary erythrocytosis which can cause symptoms of hyperviscosity, such as headaches, low energy or fatigue, blurry vision and even paresthesias. If a patient on TRT has hematocrit levels of over 54, they should consider taking measures such as reducing their dosage of testosterone, staying well hydrated and in some cases many doctors will even recommend therapeutic phlebotomy.  Elevated hematocrit has been identified as an independent risk factor for stroke, particularly when combined with high blood pressure. This is the mechanism that explains why some men on TRT can experience increased BP, as seen in Olesen et al.'s study. However, the findings from Hackett et al. indicate that hematocrit was not significantly associated with BP changes in their cohort, suggesting that the relationship may vary based on individual physiological responses. Factors like genetics, age and overall health and fitness levels as well as diet and other lifestyle factors could all potentially influence BP responses to men on TRT and need to be studied further.

Mechanisms Behind Testosterone's BP Effects

Its hard for most people to process why you can have multiple studies with differing results. The mixed findings regarding TRT and BP can potentially be attributed to several different physiological mechanisms, such as:

1. Endothelial Function Improvement: Testosterone has been shown to enhance endothelial function by reducing oxidative stress and increasing nitric oxide production, which promotes vasodilation and lowers BP. The endothelium is the thin layer of cells that line the inside of blood vessels and are key in regulating vascular health. They help to maintain blood flow, vascular tone, and overall cardiovascular function.
2. Reduction in Insulin Resistance: Some studies indicate that TRT decreases insulin resistance, a factor that is often linked to hypertension. Insulin resistance is a condition where the body's cells become less responsive to insulin, the hormone that helps to regulate blood sugar (glucose) levels.
3. Aldosterone Suppression: Testosterone may lower aldosterone levels, by reducing sodium retention in the body and thus lowering blood pressure. Aldosterone is a hormone made in the adrenal glands and helps with regulating blood pressure, sodium (salt), and potassium levels in the body. It is part of the renin-angiotensin-aldosterone system (RAAS) and works by increasing sodium and water retention (raising blood pressure), Promoting potassium excretion through urine and Autonomic Nervous System Regulation: TRT has been associated with improved autonomic function, which could contribute to better BP control.

The Impact of TRT on Enhancing the Effects of Antihypertensive Therapy

TRT’s interaction with antihypertensive medications is another important consideration for men with BP concerns who may also be on hormone therapy. The long-term study by Hackett et al. found that for men who are receiving both TRT and antihypertensive medications, BP reductions were more pronounced than for those in the placebo group. Additionally, they reported that 16.4% of men on antihypertensive therapy at baseline discontinued their medication by the study's end, which suggested an additive or synergistic effect of TRT on BP regulation based on their conclusions.

Blood Pressure Monitoring and Safety Considerations

Its hard for patients to determine the potential effect that TRT may have on their BP prior to starting treatment. So, given that the potential for TRT to both raise and lower BP depending on individual factors, monitoring by a licensed and experienced healthcare provider is essential. A solitary BP reading is often unreliable due to natural fluctuations throughout the day. To get a true idea of one’s blood pressure, there should be multiple reading throughout the day over a course of several days.  For example, the British Hypertension Society recommends a BP target of <140/90 mmHg, with ambulatory blood pressure monitoring (ABPM) being the “gold standard “for diagnosing hypertension. TRT patients should undergo regular BP assessments, including hematocrit monitoring via blood tests, to mitigate risks associated with elevated blood viscosity.

How To Determine if TRT Will Impact Your Blood Pressure

Unfortunately, as we have seen, the effects of testosterone on blood pressure in hypogonadal men is both complex and is often influenced by multiple different factors, which will include things like baseline BP, hematocrit levels, BMI, and whether a patient is concurrently on antihypertensive therapy. Men how have taken tests for low T and have been diagnosed with hypogonadism need to assess their BP as part of determine the benefits of TRT.  While some studies demonstrate a clear BP-lowering effect of TRT, particularly in men with higher baseline BP, other studies highlight the potential risk of BP elevation when taking testosterone, particularly for those patients who already have increased hematocrit levels. That’s why we recommend individualized monitoring and patient-specific management strategies for patients on TRT. These are both crucial steps for optimizing the benefits of TRT while minimizing cardiovascular risks for patients. By understanding your risk factors an experienced healthcare provider may also be able to use that information to determine the best protocol to help ensure you get the most out of your hormone therapy while minimizing risks.

Learn more about us at NovaGenix here and see how TRT can impact your life.

Wegovy & Ozempic Shortage Over: Supply Stabilizes and FDA Moves to Limit Compounded Alternatives.

 

GLP-1 Availability Shifts: FDA Actions Impact Compounded Wegovy and Ozempic After Removal From Drug Shortage List

February 21, 2025 - The landscape of GLP-1 medication availability is undergoing significant changes, with the U.S. Food and Drug Administration (FDA) announcing the resolution of shortages for key drugs like semaglutide (Wegovy and Ozempic) and tirzepatide (Zepbound and Mounjaro). These decisions have major implications for compounding pharmacies and patient access to these popular weight-loss and diabetes medications. Patients who rely on affordable medication from reputable compounding pharmacies may now be required to purchase the brand named GLP-1 medications at a considerably higher cost which may make them unaffordable to many of the same people who rely on them 

Semaglutide Shortage Resolved, Compounding Restrictions Imminent:

The FDA has officially determined that the shortage of semaglutide injection products, including Wegovy and Ozempic, is resolved. This decision follows confirmation from Novo Nordisk, the manufacturer, that their production capacity can meet current and projected national demand. While localized supply disruptions may occur as products move through the supply chain, the overall national shortage is considered over. Compounding pharmacies and organizations are determined to fight this ruling in the courts as the belief is that between diabetic patients and those who are reliant on them for weight loss, that the large manufacturers of the drugs will not be able to keep up with the demand despite their reassurances 

This resolution triggers restrictions on compounding pharmacies that have been producing versions of these drugs during the shortage. To ensure a smooth transition for patients, the FDA has provided a grace period:

• 503A Pharmacies (State-Licensed): Compounding, distribution, and dispensing of semaglutide injection products that are essentially copies of FDA-approved products is allowed for 60 calendar days from February 21, 2025, until April 22, 2025.
• 503B Outsourcing Facilities: Compounding, distribution, and dispensing of semaglutide injection products is allowed for 90 calendar days from February 21, 2025, until May 22, 2025.

Tirzepatide Shortage Also Addressed:

Similarly, the FDA has also declared the tirzepatide shortage resolved, following a re-evaluation of its previous determinations. This decision, mirroring the semaglutide action, activates similar grace periods for compounding pharmacies. Much like Wegovy and Ozempic, commercial grade Mounjaro (Tirzepatide) has been a huge breakthrough for weight loss and patients have had tremendous results while taking the subcutaneous injections. Unfortunately the grace period is about to end and many compounding pharmacies will no longer me manufacteuring these drugs which will spike the demand and costs for certain.

• 503A Pharmacies: Compounding, distributing or dispensing tirzepatide injections within 60 calendar days from December 19th 2024, until February 18, 2025.
• 503B Outsourcing Facilities: compounding, distributing or dispensing tirzepatide injections within 90 calendar days from December 19th 2024, until March 19, 2025.

It is important to note, that despite these grace periods, the FDA retains the authority to take action against compounders for violations of other statutory or regulatory requirements, particularly regarding substandard quality or unsafe products.

Impact on Compounding Pharmacies and Market Dynamics:

The FDA's decisions have significant market repercussions. Companies like Hims & Hers Health, which have heavily promoted compounded versions of GLP-1 medications, have seen substantial stock declines. The ability to produce and sell these compounded versions, which are often cheaper than brand-name drugs, is now significantly curtailed.

The Alliance for Pharmacy Compounding has raised concerns about the transition for patients currently relying on compounded medications, emphasizing the need for a smooth shift to FDA-approved alternatives.

Ongoing Monitoring of GLP-1 Availability:

The FDA continues to actively monitor the availability of other GLP-1 medications, including dulaglutide and liraglutide, which remain in shortage. The agency stresses that while manufacturers may report "available" status for certain products, this does not constitute an official FDA determination that the shortage is resolved.

Key Considerations:

• FDA Enforcement: The FDA emphasizes the legal restrictions on compounding copies of FDA-approved drugs, particularly when shortages are resolved.
• Patient Transition: Patients currently using compounded GLP-1 medications should consult with their healthcare providers to discuss transitioning to FDA-approved alternatives.
• Supply Chain Stability: While national shortages are resolved, localized supply disruptions may still occur.
• Safety and Quality: FDA-approved drugs undergo rigorous review for safety, effectiveness, and quality, whereas compounded drugs do not receive the same level of oversight but still receive quality control measures as do the pharmacies that manufacture them.

Where to Find Updates:

For the most current information on GLP-1 medication availability and drug shortages, please refer to the FDA’s Drug Shortages Database.

Estrogen Levels in Women: Understanding Its Role in Women's Health

Estrogen Levels in Women: A Key to Understanding Female Health

How Estrogen Affects Women's Health: Signs, Symptoms, and Solutions

Many women come to us with generalized symptoms of perimenopause or menopause and have questions regarding their blood work. Often, we hear questions like “What are my estrogen levels?” and “What should my estrogen levels be at for my age?” It’s important to address what estrogen is and what role it plays in women’s health.  Estrogen is a group of steroid hormones that play a crucial role in the female reproductive system and their overall health. It’s one of the major hormones that’s responsible for the development of female sexual characteristics, regulation of the menstrual cycle, and helps influence various other bodily functions. Estrogen levels naturally fluctuate throughout a woman's life, and understanding these changes is important when it comes to maintaining well-being.  

What is Estrogen?

There are three main types of estrogen in women which are primarily produced in females by the ovaries, with smaller amounts coming from the adrenal glands and fat tissue.

·         Estradiol (E2): The most potent and abundant form of estrogen, primarily produced by the ovaries playing a key role in reproductive health and is measured in blood tests to assess estrogen levels.   Normal estradiol (E2) levels in women vary depending on their age and menopausal status:   Premenopausal women: 30 to 400 pg/mL and Postmenopausal women: 0 to 30 pg/mL

Estrone (E1): A weaker form of estrogen present in lower levels than estradiol. It becomes the dominant estrogen after menopause.  Individual levels will vary from one womean to the next but here is are general ranges. Premenopausal women: 27 to 231 pg/mL  Postmenopausal women: 0 to 125 pg/mL

Estriol (E3): The weakest form of estrogen, mainly produced during pregnancy. Its role in non-pregnant women is not fully understood.   Estriol levels are typically not measured in non-pregnant women.  

What Does Estrogen Do?

The million-dollar question is “What does estrogen do?”  Estrogen exerts its effects in women by binding itself to specific receptors in various tissues throughout the woman’s body. These receptors are found in tissue and organs such as:  

• Reproductive organs: Uterus, vagina, breasts  
• Brain: Affects mood, cognition, and sleep  
• Bones: Maintains bone density and strength  
• Heart: Influences cholesterol levels and blood vessel function  
• Skin: Contributes to skin elasticity and hydration  

Estrogen Levels Throughout Life

What do normal estrogen levels look like throughout a woman’s life? As it turns out, Estrogen levels will naturally fluctuate throughout a woman's life, influenced by puberty, menstrual cycles, pregnancy, and menopause.  This can be confusing at times and even cause unwanted symptoms such as mood change, hot flashes and night sweats, menstrual cycle irregularity to name a few but don’t worry. This is completely normal and can be addressed by your healthcare provider if needed.

• Puberty: Estrogen levels rise, triggering the development of female sexual characteristics, including breasts, menstruation, and changes in body shape.  
• Menstrual cycle: Estrogen levels fluctuate throughout the menstrual cycle, peaking just before ovulation and then declining.  
• Pregnancy: Estrogen levels steadily increase during pregnancy, supporting the growth and development of the fetus and see a boost of E3.  
• Menopause: Estrogen levels significantly decline as the ovaries stop producing eggs, leading to various physical and emotional changes and E1 becomes the dominant form of estrogen.  

Normal Estrogen Levels

Normal estrogen levels vary depending on age and menopausal status. Here's a general guideline for estradiol (E2) levels:

Premenopausal women: 30 to 400 pg/mL  

Postmenopausal women: 0 to 30 pg/mL  

It's important to note that these are just general ranges, and individual levels may vary.  Also keep in mind that these number will fluctuate and every patient is unique so if you suspect there may be an issue with your hormones, speak to your doctor about your concerns.  A healthcare provider can interpret estrogen levels in the context of a woman's overall health and medical history.

Effects of Low Estrogen

Low estrogen levels can lead to various symptoms, including:

• Menstrual irregularities: Changes in cycle length, flow, or missed periods  
• Hot flashes: Sudden feelings of warmth, sweating, and flushing  
• Vaginal dryness: Discomfort during intercourse  
• Sleep disturbances: Difficulty falling asleep or staying asleep  
• Mood changes: Irritability, anxiety, or depression  
• Decreased libido: Reduced sexual desire  in women
• Bone loss: Increased risk of osteoporosis
• Cognitive changes: Difficulty concentrating or remembering things

Estrogen Replacement Therapy (ERT)

Hormone Replacement Therapy for women is a very common treatment option for women experiencing the unwanted signs and symptoms of perimenopause of menopause. It often includes estrogen, testosterone and progesterone. Estrogen replacement therapy (ERT) in particular involves taking medication to increase estrogen levels back to an optimal level for the patient. It is primarily used to manage menopausal symptoms and prevent bone loss. ERT can be delivered in various forms, including:  

• Oral tablets: The most common form of ERT. These are generally best taken after a meal to reduce the risk of stomach upset and improve absorption. Some women find it helpful to take them in the morning to maintain consistent hormone levels throughout the day.
• Transdermal patches: Applied to the skin, delivering estrogen directly into the bloodstream. These are typically replaced every few days. The time of day for application is less critical, but it's important to choose a consistent time and location for each application.  
• Topical gels or creams: Applied to the vagina or vulva. The time of day for application may depend on the specific product and individual needs.
• Vaginal rings: Inserted into the vagina, releasing estrogen over time. They provide a continuous release of hormones.

Benefits of ERT for Women

ERT can provide several benefits, including:

• Relief from menopausal symptoms: Reduces hot flashes, vaginal dryness, sleep disturbances, and mood changes  
• Prevention of bone loss: Helps maintain bone density and reduce the risk of osteoporosis  
• Improved quality of life: Enhances overall well-being and reduces the impact of menopausal symptoms  

Risks of ERT

Like all medications and medical treatments ERT also carries potential risks, including:

• Increased risk of certain cancers: ERT may increase the risk of breast cancer and endometrial cancer so it’s important to get screened. The U.S. Preventive Services Task Force (USPSTF) recommends that women aged 40 to 74 years with average risk get screened every 2 years, however, the American Cancer Society (ACS), recommend annual mammograms starting at age 45, or even 40, depending on individual risk factors and preferences.   Higher risk patients with a family history of breast cancer should get tested more frequently.
• Increased risk of blood clots: May increase the risk of deep vein thrombosis and pulmonary embolism  
• Possible Increased risk of stroke and heart attack: ERT May increase the risk of cardiovascular events, especially in women with existing risk factors. Studies on the relationship between ERT and CVD have yielded mixed results. Some studies have shown an increased risk of heart attack, stroke, and blood clots in women taking ERT, while others have not found a significant association. Its important to discuss whether you’re in a high risk category for your age, overall health, family history and time since the onset of menopause to determine if there is an increased risk.

Who Should Consider ERT?

ERT is not suitable for all women. It is important to discuss the benefits and risks with a licensed and experienced healthcare provider to determine if it is appropriate for you. There are several factors to consider including:

• Severity of menopausal symptoms: ERT may be more beneficial for women with severe symptoms that significantly impact their quality of life. Oten mild symptoms subside fairly quickly for many women.
• Risk factors for certain cancers: Women with a personal or family history of breast cancer or endometrial cancer may have an increased risk with ERT and should weigh the risk/reward of HRT.
• Risk factors for cardiovascular disease: Women with existing heart disease or risk factors for cardiovascular disease may have an increased risk with ERT and should look for other ways to alleviate symptoms first.

Alternatives to ERT

There are alternative treatments for managing menopausal symptoms and preventing bone loss for women, including:

• Lifestyle changes: Regular exercise, a healthy diet, and stress management can help alleviate menopausal symptoms. Strength training in particular is beneficial. Strength training can stimulate the production and balance of various hormones, including growth hormone, testosterone, and estrogen. This can help alleviate symptoms associated with hormone imbalances, such as mood swings, fatigue, and weight gain.  
• Non-hormonal medications: Certain medications can help reduce hot flashes and improve sleep.   These medications work through different mechanisms than hormone replacement therapy (HRT) and may be suitable for women who cannot or choose not to take HRT.  

Here are some common non-hormonal medications used for hot flashes and sleep problems during menopause:

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs): These antidepressants can also help reduce hot flashes. Examples include paroxetine (Brisdelle), venlafaxine (Effexor XR), and desvenlafaxine (Pristiq).  

Gabapentinoids: Gabapentin (Neurontin, Gralise) and pregabalin (Lyrica) are anti-seizure medications that can also reduce hot flashes. Gabapentin can also improve sleep quality.  

Clonidine: This medication, typically used to treat high blood pressure, can also help reduce hot flashes.  

Fezolinetant (Veozah): This is a newer non-hormonal medication specifically for hot flashes. It works by blocking a pathway in the brain that helps regulate body temperature.  

It's important to note that these medications may have side effects, and their effectiveness can vary among individuals. It's crucial to discuss the benefits and risks of each medication with a healthcare provider to determine the most appropriate treatment plan.

 

• Herbal remedies: Several herbal remedies have been traditionally used to manage hot flashes and sleep problems during menopause. However, it's important to note that the effectiveness and safety of these remedies can vary, and scientific evidence supporting their use may be limited. It's crucial to consult with a doctor before trying any herbal remedy, as they may interact with other medications or have potential side effects. This list is not intended as an endorsement of any herbal remedy or to treat any symptoms but instead is for informational purposes as to how menopause symptoms have been treated without using hormone therapy. Here are some commonly used herbal remedies for hot flashes and sleep problems during menopause:

Black cohosh: This herb has been traditionally used to relieve hot flashes, night sweats, and other menopausal symptoms. However, studies on its effectiveness have yielded mixed results.  

Red clover: Red clover contains isoflavones, which are plant-based compounds that can mimic estrogen's effects. Some studies suggest that red clover may help reduce hot flashes.  

Soy: Soybeans are rich in isoflavones and may help alleviate hot flashes and improve sleep quality.  

Evening primrose oil: This oil contains gamma-linolenic acid, which may help regulate hormone levels and reduce hot flashes. However, scientific evidence supporting its use is limited.  

Valerian root: Valerian root has been traditionally used to promote relaxation and improve sleep quality. It may be helpful for women experiencing sleep problems during menopause.  

Sage: Sage has been used to reduce hot flashes and night sweats. Some studies suggest that it may be effective in alleviating these symptoms.  

It's important to choose high-quality herbal supplements from reputable brands and follow recommended dosages. Be aware of any potential side effects or interactions with other medications. If you experience any adverse reactions, discontinue use and consult with a healthcare provider.

As women age, they start to experience changes and often these changes can be directly attributed to hormonal health. Estrogen in particular plays a vital role in women's health throughout their lives. Understanding estrogen levels and their fluctuations is essential for maintaining well-being and improving quality of life. ERT can be an effective treatment for managing menopausal symptoms and preventing bone loss, but it is important to discuss the benefits and risks with a healthcare provider to determine if it is appropriate.   For more information visit us online or call to schedule an appointment to speak with our physician Dr. Timothy W. Mackey.