Hormone Replacement Therapy & Progesterone: How This Hormone Can Help Women in Menopause

Progesterone's Role in HRT for Menopausal Women: Understanding Levels, Effects, and Safety 

Hormone Replacement Therapy (HRT) offers significant support to women navigating the challenging symptoms of menopause, aiming to enhance their well-being during this transitional phase. A delicate interplay of hormones, including estrogen, progesterone, prolactin, hCG, FSH, LH, T3/T4, and testosterone governs women's mental and physical health. The hormonal fluctuations characteristic of perimenopause can disrupt this balance, leading to distressing symptoms like hot flashes, night sweats, mood changes, vaginal dryness, and sleep disturbances, prompting women to seek guidance from healthcare professionals. Among these crucial hormones, progesterone plays a vital role, often in concert with estrogen, and understanding its optimal levels, physiological functions, and the implications of imbalance is key to successful HRT. This article will explore progesterone's role in HRT, focusing on ideal levels, its impact on women's health, the effects of deficiency, and menopausal changes.

Progesterone's Role in Supporting Women’s Health Across All Stages of Life

Progesterone, a crucial steroid hormone, is predominantly synthesized in women by the ovaries' corpus luteum following ovulation. Its primary function centers around preparing the uterus for potential pregnancy by promoting the thickening of the endometrial lining. This vital role extends to supporting pregnancy itself, as evidenced by its use in IVF treatments to aid implantation and fetal development. However, progesterone's influence extends beyond reproduction, impacting a range of physiological processes within the female body.  

Progesterone's best-known function likely involves endometrial regulation (endometrium), its interaction with the uterine lining crucial for the menstrual cycle, pregnancy, and female reproductive health. It works against estrogen's growth-promoting actions, preventing excessive endometrial thickening and helping lower the risk of hyperplasia and cancer, a key consideration in estrogen-based Hormone Replacement Therapy (HRT). Furthermore, progesterone exhibits neuroprotective qualities, demonstrating calming and anxiety-reducing (anxiolytic) effects. It can also aid in mood stabilization and improve sleep quality, common concerns during perimenopause and menopause. Notably, progesterone interacts with GABA receptors  in the brain, which play vital roles in promoting relaxation by dampening excitatory signals, regulating sleep by inhibiting overactive neurons, controlling muscle tone, and modulating mood and emotion – often significantly impacted by hormonal fluctuations. Beyond these effects, progesterone stimulates osteoblasts, the cells responsible for bone formation, promoting new bone growth and counteracting age-related bone loss, especially after menopause. Finally, while its impact on cardiovascular health is intricate and ongoingly studied, research suggests progesterone may offer some benefits, including vasodilation and potentially positive changes in cholesterol and lipid profiles.

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

Determining "good" progesterone levels in HRT is a complex question without a universal answer. Unlike estrogen with its often-defined target ranges, ideal progesterone levels in HRT are patient-specific and depend on context. What constitutes a "good" level varies based on HRT type, administration method (oral, transdermal, vaginal), and individual symptoms and risk factors. Women have unique baseline progesterone levels influenced by age, menopausal status, and overall health, impacting their needs. Some may require higher doses for endometrial protection, while others need lower doses to minimize side effects. Furthermore, the HRT regimen—sequential (cyclical progesterone administration) versus continuous combined (daily progesterone and estrogen)—affects target levels, differing between these approaches.

Absorption varies with progesterone type, influencing dosage based on medication and targeted symptoms. Oral progesterone, like micronized progesterone, has systemic effects and is often prescribed for sleep and anxiety. For many HRT patients, the primary goal is endometrial protection, requiring sufficient progesterone levels to counteract estrogen-induced hyperplasia, often achieved with bioidentical micronized progesterone (Prometrium) due to its effectiveness and tolerability, potentially offering sleep and anxiety benefits and a lower blood clot risk compared to synthetics. However, it may cause drowsiness and, in some, bloating or dizziness. Typical oral dosage ranges from 100–200 mg at bedtime, individualized by the physician. Topical or Transdermal Progesterone may have inconsistent absorption and might not adequately protect the endometrium. In contrast, vaginal progesterone (suppositories) is directly absorbed by the uterus and is commonly used in IVF and fertility treatments. 

How are Progesterone levels tested?

Determining the optimal method for checking hormone levels depends on the individual patient; the two main options are serum versus salivary levels. A blood test (serum progesterone test) is the most common approach. Progesterone levels measured in blood can assist healthcare providers in evaluating ovulation, fertility, pregnancy health, and overall hormone balance. These tests are typically conducted: during the mid-luteal phase (days 21-23 of a 28-day cycle) to confirm ovulation; during early pregnancy to assess sufficient progesterone for support; and when on HRT to monitor medication effectiveness and progesterone balance in therapy.

• 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 the more common choice in clinical settings. Low levels may suggest  anovulation, luteal phase defects, or hormonal imbalances, while high levels can occur in pregnancy, with ovarian cysts, or from excessive progesterone supplementation. Blood tests are generally considered the most reliable method for assessing progesterone levels in most medical contexts. Saliva or urine tests might offer some information but are typically less reliable for diagnosing hormone imbalances or guiding HRT adjustments and are often not considered dependable for clinical testing. While specific target ranges differ, the aim in HRT is to ensure sufficient progesterone to prevent endometrial hyperplasia. A mid-luteal phase serum progesterone level is often the goal for cyclical HRT, whereas lower levels may be acceptable for continuous combined HRT. Ultimately, HRT necessitates an individualized approach, and the optimal progesterone level should be determined by a healthcare provider through careful patient assessment and monitoring.

Consequences of Low Progesterone Levels

Insufficient progesterone levels, particularly within HRT, can potentially result in several adverse effects, including: Endometrial Hyperplasia, the most significant risk, involving abnormal thickening of the uterine lining that may progress to endometrial cancer if unmanaged. Breakthrough Bleeding, characterized by irregular or heavy menstrual bleeding, especially in sequential HRT regimens. Mood Disturbances, where reduced calming effects of progesterone can lead to heightened anxiety, irritability, and mood swings. Sleep Disruption, where low progesterone can contribute to insomnia and poor sleep quality, potentially worsening hormonal fluctuations.

Progesterone and Menopause

Perimenopause and menopause mark a significant period of bodily adjustment for women as ovarian production of estrogen and progesterone gradually ceases. This hormonal decline triggers a range of symptoms and physiological changes. Notably, progesterone levels drop significantly during perimenopause and become very low post-menopause due to the cessation of ovulation, the primary source of progesterone synthesis. This decline typically leads to a thinning of the uterine endometrial lining. The combined reduction in both estrogen and progesterone contributes to common menopausal symptoms like hot flashes, night sweats, mood swings, and vaginal dryness. Hormone Replacement Therapy (HRT) aims to alleviate these symptoms and improve quality of life by replacing declining hormones. Progesterone is crucial in HRT, especially for women with a uterus, to balance estrogen's effects and prevent endometrial hyperplasia.

Optimizing Progesterone Levels on HRT

Achieving optimal progesterone levels on HRT often involves a period of individual adjustments. Effective hormone replacement therapy for women management necessitates collaboration between patient and provider, including follow-up bloodwork to evaluate treatment effectiveness on hormone levels and symptom relief. Regular monitoring of hormone levels and endometrial health is a prudent approach to women's HRT, crucial for ensuring "good" progesterone levels and preventing complications. Individualized dosing is vital, as HRT regimens must be tailored to meet each patient's unique needs and consider risk factors before establishing a protocol and dispensing medication. Open communication with your doctor regarding symptoms, concerns, and potential side effects is essential; a good approach and supportive healthcare team help ensure both the efficacy and safety of the HRT protocol.

So basically, progesterone is an indispensable hormone in HRT, crucially protecting the endometrium and contributing to women's overall well-being. Comprehending its roles, ideal levels, and the implications of imbalances is key to effective HRT management. Collaborating closely with healthcare providers, adopting a holistic approach, and maintaining healthy lifestyle habits—including a balanced diet, regular exercise, and stress management—can further support hormonal balance. With a knowledgeable approach, women can navigate menopause with increased confidence and enhanced 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.