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GENEMEDICS NUTRITION

Progesterone
Friday, August 16th, 2019

Progesterone is a natural steroid found in much higher concentrations in women. This hormone belongs to the family of hormones known as progestogens and is involved in several bodily functions such as menstrual cycle, formation of the embryo, and pregnancy. Progesterone is produced and released by the ovaries and it works harmoniously with the hormone estrogen in maintaining fertility in women.

Overall Health Benefits of Progesterone

Progesterone in Women

Progesterone’s main functions are associated with the maintenance of the female reproductive system. The levels of this hormone are known to surge during ovulation, marking the peak of fertility. At healthy levels, progesterone plays the following important roles in women’s body:

  • Maintains the uterine lining and prevents build-up of excessive tissues. [1-4]
  • Produces breast milk. [5]
  • Maintains healthy pregnancy. [6-8]
  • Decreases contractility of the uterine smooth muscle. [9]
  • Releases egg from the ovaries during ovulation. [10-12]

Progesterone in Men

Just like estrogen, progesterone is also present in men in smaller amounts. Progesterone in men is produced in the testes and adrenal glands. Unlike in women, men’s progesterone levels do not vary on a cycle, although there are various factors like diet, stress and lifestyle that can significantly affect the production of progesterone. This hormone has several important effects in men such as the following:

  • Increases body temperature [13-15]
  • Relaxes smooth muscles [16-18]
  • Guards against osteoporosis and other bone problems [19-21]
  • Maintains prostate health [22-23]
  • Preserves masculinity [24-25]

Progesterone Deficiency

Progesterone is a precursor to the hormones testosterone and estrogen. Falling progesterone levels can also cause these hormones to diminish, which can have detrimental effect on health. The levels of progesterone are relatively low prior to ovulation, and they usually spike when the ovaries release an egg. Elevated levels of progesterone remain for several days and either continues to remain elevated if pregnancy occurs, or drop during menstrual cycle.

Progesterone levels may fall because of several medical conditions such as the following:

  • Amenorrhea (abnormal absence of menstruation)
  • Decreased function of the ovaries
  • Ectopic pregnancy (pregnancy outside the lining of the uterus)
  • Miscarriage
  • Preeclampsia (characterized by high blood pressure and protein in the urine)
  • Toxemia (blood poisoning)

In women who are not pregnant, falling progesterone levels can lead to the following signs and symptoms:

  • Abnormal uterine bleeding
  • Headaches or migraines
  • Hot flashes
  • Irregular or absent menstruation
  • Low sex drive
  • Mood changes, including anxiety or depression

On the other hand, pregnant women with low progesterone levels may experience the following signs and symptoms:

  • Abdominal pain
  • Constant breast tenderness
  • Extreme fatigue
  • Low blood sugar levels (hypoglycaemia)
  • Vaginal spotting

In men, signs and symptoms of low progesterone include:

  • Bone loss
  • Depression
  • Erectile dysfunction
  • Fatigue
  • Gynecomastia (breast enlargement)
  • Hair loss (alopecia)
  • Loss of muscle mass and strength
  • Low libido
  • Weight gain

Progesterone levels can also spike at dangerous levels causing detrimental effects on health. This condition can lead to:

  • Bloating
  • Breast tenderness
  • Depression
  • Dizziness
  • Estrogen deficiency
  • Extreme fatigue
  • Lack of interest in sex
  • Mood swings
  • Muscle Weakness
  • Ovarian cysts
  • Sleepiness
  • Vaginal dryness

In order to diagnose progesterone imbalance, a qualified hormone replacement therapy doctor will order a blood test. The results can help determine the cause of infertility, help monitor pregnancy health, help diagnose abnormal uterine bleeding, and correct any medical condition related to low or high progesterone levels.

Proven Health Benefits of Progesterone Replacement Therapy (PRT)

Most highly trained and qualified doctors will prescribe PRT in order to treat signs and symptoms of progesterone deficiency. Progesterone medications called progestins are usually produced in the laboratory and are prescribed for those with progesterone deficiency. These synthetic steroid hormones have progesterone-like properties and are available as capsules, creams, vaginal gels, implants, injections, and intrauterine devices (IUD). The health benefits of PRT are backed by an overwhelming body of clinical research, making it an effective therapeutic option for various age-related medical maladies.

Fights Inflammation

Progesterone has potent anti-inflammatory properties that can help treat and prevent a wide array of inflammatory conditions. Numerous clinical trials suggest that progesterone fights inflammation through the following important mechanisms:

  1. It suppresses NF-κB and MAPK activation, which in turn inhibits the production of proinflammatory markers like COX-2, IL-6, iNOS, and TNF-α. [26-31]
  2. It enhances the synthesis of brain steroids. [32]
  3. It inhibits vascular permeability and the formation of granulation tissue in the early phase of the inflammation. [33]
  4. It reduces cellular inflammatory response. [34]

Promotes Weight Loss

Progesterone can also help prevent the detrimental effects of obesity on health by promoting weight loss and reducing total body fat percentage. There is mounting evidence that progesterone can help you achieve a healthier weight:

  1. In obese men, higher progesterone levels are associated with lower body mass index (BMI) and reduced waist circumference. [35]
  2. Progesterone promotes weight loss by reducing fluid retention. [36]
  3. Progesterone promotes weight loss by decreasing fat stores. [37]
  4. Loss of body weight is associated with higher levels of progesterone. [38]
  5. Progesterone lowers one’s risk of developing obesity by preventing estrogen dominance. [39-42]

Lowers Blood Pressure

Progesterone also has potent antihypertensive properties that can help bring down blood pressure to healthy levels. Numerous clinical trials support this beneficial effect of progesterone:

  1. In postmenopausal women with high blood pressure, progesterone supplementation lowers blood pressure by 6 to 7 mm Hg. [43-44]
  2. Progesterone exerts its antihypertensive effect by reducing mean arterial pressure. [45]
  3. In postmenopausal women, the use of progesterone supplements is associated with lower blood pressure. [46]
  4. Progesterone lowers blood pressure by promoting sodium loss and excretion of renin (a substance that increases blood pressure). [47]

Normalizes Blood Sugar Levels

In both men and women, low progesterone levels may lead to insulin resistance, a condition in which the body doesn’t normally respond to the effects of insulin. If left untreated, insulin resistance can cause fatal diseases including diabetes, cancer, stroke, heart failure, and other debilitating conditions. Evidence suggests that progesterone reduces insulin and regulates blood sugar levels, thereby improving overall health:

  1. In healthy women and women with premenstrual syndrome, increased progesterone levels are associated with lower blood sugar levels. [48]
  2. Progesterone has a major role in controlling blood sugar levels possibly by affecting the levels of nitric oxide, a compound that helps improve blood circulation. [49]
  3. Progesterone helps lower blood sugar levels by making more storage of glycogen, the principal storage form of glucose. [50]
  4. In women, progesterone improves blood sugar metabolism. [51]
  5. In animal models of diabetes, progesterone therapy normalizes blood sugar levels. [52]

Improves Libido

Progesterone modulates sexual desire or libido in women. The age-related gradual decline in ovarian function decreases the levels of progesterone, accompanied by decreased sexual desire in large portion of postmenopausal women. Studies show that progesterone therapy can help ramp up sexual power in women, thus restoring sexual vitality and improving sexual function:

  1. In menopausal women, PRT relieves vaginal dryness. [53-54]
  2. In postmenopausal women, PRT reduces the biological causes of loss of libido. [55]
  3. In postmenopausal women, PRT improves frequency of fantasy, masturbation, or female-initiated coitus. [56]
  4. In postmenopausal women, PRT increases self-reported sexual desire. [57]

Maintains Bone Health

Progesterone stimulates bone growth through several important mechanisms. Several lines of evidence suggest that progesterone supplementation can help maintain bone health:

  1. In human bone cells, the administration of progesterone promotes bone formation by activating bone forming cells (osteoblasts). [58-60]
  2. In postmenopausal women, progesterone supplementation decreases the risk of fractures. [61]
  3. In postmenopausal women who had surgical removal of the uterus (hysterectomy), progesterone supplementation prevents osteoporotic fractures. [62-63]
  4. In healthy women experiencing problems with fertility, progesterone supplementation increases bone mineral density (BMD). [64]
  5. Progesterone improves bone health by interacting with bone-related molecules such as sclerostin, vascular endothelial growth factor (VEGF), and basic fibroblast growth factor (bFGF). [65-66]
  6. In early postmenopausal women, progesterone supplementation prevents bone loss by decreasing bone breakdown. [67]
  7. When combined with medications for bone loss, progesterone exerts greater increases in BMD. [68-70]

Protects against Various Types of Cancers

Progesterone can boost one’s health with its anti-cancer properties. There is increasing evidence that this powerful hormone can help protect against one of the most deadly diseases in the world:

  1. In the uterus, progesterone stops the growth of abnormal tissues. [71]
  2. In obese and postmenopausal women, progesterone deficiency increases risk for endometrial cancer, suggesting that healthy levels of progesterone exerts anti-cancer properties. [72-76]
  3. In women with uterine enlargement and cysts, progesterone supplementation is beneficial in treating abnormal tissue growths. [77-93]
  4. In patients with advanced or recurrent endometrial cancer, progesterone treatment displays beneficial effects. [94-98]
  5. Progesterone treatment combats cancer by inhibiting cell growth and invasion. [99-101]
  6. Progesterone inhibits the growth of breast cancer cells by fighting inflammation. [102-103]
  7. In rats, progesterone inhibits the growth of tumors through multiple pathways. [104]

Improves Mood

Stressful situations as well as advancing age can lead to low mood in both men and women. Interestingly, there is strong scientific evidence that supports the mood-enhancing effects of progesterone:

  1. In women with symptoms of premenstrual syndrome (PMS), administration of the synthetic progesterone called progestin decreases anxiety. [105-107]
  2. In women with depression associated with childbirth, progesterone administration successfully improves depressive symptoms. [108-114]
  3. In healthy female volunteers, higher level of progesterone is associated with reduced fatigue, confusion and other markers of anxiety. [115]
  4. Progesterone helps improve mood by increasing the levels of brain chemicals (neurotransmitters) such as dopamine and serotonin. [116-127]
  5. Progesterone prevents depression-like behaviour in animal models of Parkinson’s disease by improving cognitive function. [128]
  6. In rat models, progesterone significantly reduces anxiety behaviour. [129-135]

Improves Sleep Quality

Aging, certain medical conditions, lifestyle, and other factors can significantly affect sleeping pattern and sleep quality. Aside from lifestyle modifications, doctors also prescribe PRT for patients with sleeping difficulties. There is mounting evidence that progesterone administration can help achieve a restful sleep:

  1. In men and women with sleeping problems like obstructive sleep apnea and obesity-hypoventilation, progesterone exerts a sleep induction or hypnotic effect. [136-137]
  2. In postmenopausal women with sleep disturbances, PRT restores normal sleep pattern. [138]
  3. In postmenopausal women, administration of medroxyprogesterone acetate and micronized progesterone are both effective in treating menopausal symptoms as well as improving sleep quality. [139]
  4. In healthy men, progesterone administration significantly increases the amount of non-rapid eye movement (REM) sleep, which is one of the deepest cycles of sleep. [140]
  5. In healthy postmenopausal women, progesterone reduces wakefulness. [141]
  6. In women with obstructive sleep apnea (OSA), low levels of progesterone were seen. [142]
  7. In animal models, progesterone modulates spontaneous sleep patterns and recovery from sleep deprivation. [143-144]

Relieves Menopausal Symptoms

Menopause marks the end of the menstruation period and it’s diagnosed after you don’t have any menses after a year. While menopause is a natural biological process, it can cause various physical symptoms such as hot flashes, vaginal dryness, chills, night sweats, sleep problems, weight gain, dry skin, thinning of hair and mood changes. Fortunately, there are many effective treatments available, from lifestyle modifications to PRT, and studies show that restoring progesterone to healthy levels can help improve the quality of life of menopausal women:

  1. Progesterone administration in menopausal women relieves hot flushes, mood swings, sleeping difficulties, night sweats, vaginal dryness and restlessness. [145]
  2. In menopausal women, progesterone administration effectively corrects progesterone deficiency as well as menopausal symptoms. [146]
  3. Progesterone administration in menopausal women relieves breast tenderness. [147-148]
  4. In postmenopausal women, administration of transdermal progesterone at a daily dose of 20 mg significantly relieves menopausal symptoms without any adverse side effects. [149]
  5. In healthy postmenopausal women, progesterone administration at varying doses improves menopausal symptoms as well as quality of life. [150]
  6. In postmenopausal women with severe menopausal symptoms, administration of progesterone cream at varying doses (60, 40, 20, or 5 mg) significantly relieves symptoms and improves physical and social functioning. [151]
  7. In healthy postmenopausal women, administration of progesterone cream (20 mg) daily significantly treats vasomotor symptoms (night sweats and hot flashes). [152]
  8. In perimenopausal women, progesterone demonstrates great promise in the treatment of climacteric symptoms (hot flashes, sweating, and vaginal dryness). [153]
  9. In early postmenopausal women, progesterone improves menopausal symptoms such as vasomotor and sexual dysfunction symptoms without any adverse side effects. [154]
  10. In postmenopausal women, low-dose monthly intramuscular injections of progesterone are effective at reducing menopausal symptoms at short-term with a low rate of adverse events. [155]
  11. In postmenopausal women, administration of progesterone decreases breathing irregularities, arousal from sleep, anxiety, and memory impairment. [156]
  12. Low progesterone results in uncontrolled menstrual bleeding, whereas progesterone administration reduces bleeding. [157]

Maintains Fertility

Progesterone is known as the “hormone of pregnancy” because it plays several important bodily functions during this stage such as maintenance of the lining of the uterus, survival of the embryo, prevention of immune rejection of the developing baby, development of the fetus, and proper utilization of fat and energy. Because of these vital functions, several studies assessing the beneficial effects of progesterone supplementation on fertility issues have been performed and results indicate that progesterone is safe and effective:

  1. Women with low progesterone levels are at greater risk for unexplained miscarriages whereas women who received progesterone treatment had reduced rate of miscarriages. [158-162]
  2. Progesterone helps maintain early pregnancy by decreasing inflammation. [163-167]
  3. Intramuscular or vaginal progesterone administration improves pregnancy outcome by supporting the luteal phase (thickening of the uterus in preparation for pregnancy) following in-vitro fertilization and is widely employed in intrauterine insemination cycles as well. [168-173]
  4. Progesterone supplementation during the luteal phase and in early pregnancy can successfully treat infertility. [174]
  5. In women with fertility issues, artificial use of progesterone helps achieve normal development of the uterus. [175-176]
  6. Progesterone supplementation is associated with higher delivery rates. [177-178]

Improves Muscle Mass

Progesterone is not only a hormone that maintains the reproductive system. Scientific research found that this versatile hormone can also help build muscle mass, prevent muscle wasting related to chronic diseases, and improve body composition especially in the elderly:

  1. In postmenopausal women, progesterone improves muscle mass by increasing muscle protein synthesis rate by as much as 50%. [179-180]
  2. Progesterone increases the activity of MYOD1 gene, which helps increase muscle mass. [181-182]
  3. In postmenopausal women, administration of the synthetic progesterone progestin increases muscle mass and strength. [183]
  4. In nonmenopausal women, progesterone increases skeletal muscle mass. [184]
  5. In rats, progesterone supplementation prevents muscle inflammation after strenuous exercise, thus preventing muscle damage that can lead to muscle wasting. [185]
  6. Progesterone helps maintain the neuromuscular system by modulating the growth and development of bone, cartilage, ligament, and muscle fibers. [186-187]
  7. In rats, progesterone regulates the growth of fat-free tissues and skeletal muscle mass. [188]

Reverses Hair Loss

Hair loss or “alopecia” is characterized by hair thinning or loss of hair from the head or body. While hair loss is a natural body process, certain factors such as stress, medication, genes, and hormonal imbalance can result in baldness. Today, many effective alternative treatments such as hormone therapy are being prescribed for hair loss. Latest research shows that progesterone therapy can help regrow hair and prevent age-related baldness:

  1. At high doses, progesterone inhibits the enzyme 5-alpha reductase, and prevents the body from converting testosterone to dihydrotestosterone (DHT).  [189-191] Increased levels of 5-alpha reductase and DHT can damage hair follicles and accelerate hair loss. [192-193]
  2. Hair loss after giving birth is common in women with low progesterone levels, thus, restoring progesterone to healthy levels can be beneficial. [194]

Maintains Healthy, Younger Skin

Progesterone levels start to decline during mid to late 30’s, which leaves the skin looking dull and old. Interestingly, stronger scientific evidence suggests that this revitalizing hormone is beneficial for skin elasticity and circulation, making it an effective anti-aging treatment:

  1. In postmenopausal women, application of progesterone cream improves skin elasticity and reduces more wrinkles. [195]
  2. In women, progesterone administration helps maintain healthy, younger skin by improving blood circulation. [196]
  3. In menopausal women, administration of progesterone vaginal suppository significantly improves skin moisture, elasticity and skin thickness. [197]

Protects and Repairs Nerve Cells

Progesterone is classified as a “neurosteroid” because of its many critical functions in the nervous system. Among them, protecting the brain from injury and promoting repair of nerve cells (neurons) makes progesterone an important hormone in the maintenance of nerve health. In fact, numerous research studies attest to the neuroprotective effects of progesterone:

  1. Progesterone improves the integrity and function of nerve tissues in the brain. [198]
  2. Progesterone stimulates the growth of nerve cells, accelerates the maturation of the regenerating axon (long threadlike part of a nerve cell), and enhances the creation of protective outer covering of nerve fibers known as “myelin sheath”. [199-202]
  3. In patients with traumatic brain injury (TBI), progesterone enhances the repair of injured brain nerve cells by preventing inflammation, reducing oxidative stress, inhibiting programmed cell death (apoptosis), and preventing excessive stimulation of nerves. [203-231]
  4. In animal models, progesterone promotes faster regeneration of injured nerve fibers. [232]
  5. In aged rats, progesterone reduces myelin fiber abnormalities and myelin fiber loss in the sciatic nerve. [233]
  6. In rats, progesterone increases the extent of myelin sheath formation in the injured nerves. [234-241]
  7. Progesterone helps maintain nerve health by increasing the levels of nerve growth factor (NGF). [242]
  8. In dogs, progesterone accelerates the regeneration of injured sciatic nerve. [243]
  9. In rat models of sciatic nerve constriction, progesterone prevents allodynia (pain from stimuli which are not normally painful). [244]

Detoxifies the Body

Progesterone is known as a “natural diuretic”, which means that it helps the body get rid of toxins by increasing urination. Stronger scientific evidence supports the detoxifying effect of progesterone:

  1. In healthy women, administration of progesterone increases glomerular filtration rate (filtering ability of the kidneys), uric acid clearance, and excretion of other body toxins. [245]
  2. Progesterone increases the excretion of excessive calcium and phosphorus, thereby preventing kidney stones. [246]
  3. Progesterone promotes urination while improving body water distribution. [247]

Relieves Headaches and Migraines

For many women who are experiencing headaches, migraines may become more frequent and severe as they approach their menopausal years. This is because hormone levels fluctuate unevenly. While headaches and migraines during this time period can be debilitating, studies show that progesterone administration can be beneficial:

  1. In majority of women, progesterone administration has a positive effect on the course of both migraines with aura (MA) and without aura (MO). [248]
  2. Progesterone-only contraceptives are considered safe and effective in alleviating migraines in women. [249]
  3. Progesterone therapy can be safely prescribed for women suffering from various types of headaches without any contraindications. [250]

Boosts Immune Function

Progesterone has been shown to have direct effects on immune cells, thereby boosting the immune function. Evidence suggests that progesterone can be beneficial in maintaining the immune health through various important mechanisms:

  1. Progesterone inhibits the production of proinflammatory markers like COX-2, IL-6, iNOS, and TNF-α. [251-256]
  2. Progesterone regulates the activity of natural killer (NK) cells of the immune system.
  3. Progesterone modulates the activity of the T cells of the immune system. [258]
  4. At pregnancy levels, progesterone may suppress disease activity in rheumatoid arthritis and multiple sclerosis. [259]
  5. In healthy pregnant women, progesterone boosts immune function by raising the levels of antibodies. [260-261]

The Women’s Health Initiative (WHI) Study Decoded

In 2002, the results of the large Women’s Health Initiative (WHI) study have been controversial. As one of the largest clinical trials assessing the safety and efficacy of progesterone on women, the authors of the WHI study concluded that progestin plus estrogen administration can increase one’s risk of developing breast cancer, heart disease, stroke, blood clots, and overall harm, which led to early stoppage of the clinical trial. [262] However, a large body of clinical trials and other authors do not agree with the results of the WHI study because of the following reasons:

  1. The hazard ratio (HR) of the WHI study did not reach statistical significance. Other health experts suggest that the potential health hazards found in the in the estrogen-plus-progestin trial did not reach statistical significance and was based on unadjusted risk hazards. [263-264] In addition, some findings differed for women by age group and years since menopause.
  2. The WHI study does not even qualify as a randomized placebo-controlled study.

The reasons for this are the following: [265-269]

  1. After randomization, the women were free to decide whether to continue their assigned treatment or whether to undergo diagnostic procedures.
  2. Almost 50% of the women were aware of their treatment.
  3. The participants received several warnings regarding increased risks of heart disease, stroke and blood clots during the study.
  4. The authors of the WHI study did not mention the other significant benefits of estrogen-plus-progestin treatment among the participants. The authors did not mention that the treatment “significantly” decreased the risk of colon cancer and hip fractures (about a 33% reduction) among the participants. [270]
  5. There are some health factors that might have altered the outcome of the WHI study. The participants in the WHI study has an average BMI of 28 (overweight), one-third were hypertensive and one-half were smokers, suggesting that these factors might have significantly altered the outcome of the clinical trial. [271]
  6. The women in the WHI study were 12-15 years past the onset of menopause. This means that the participants were without their premenopausal progesterone levels long enough to bring about various changes in bodily functions.
  7. The WHI study actually found beneficial effects of estrogen-plus-progestin on various health hazards. The authors of the WHI study found the following beneficial effects of estrogen-plus-progestin administration: [272]
  • Diabetes risk decreased by 14-19%.
  • In women ages 50-54 years, hot flashes and night sweats were decreased by 64%.
  • Joint pain decreased during treatment.

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