What is the difference between Progesterone and Synthetic Progestins (provera or medroxyprogesterone?

Progesterone and Provera are two vastly different compounds with different effects in the body. Every cell in the body, including bone, heart, brain, and breasts, have progesterone receptors. Synthetic progestins (provera) are unable to balance the effect of estrogen dominance in the body and even contribute to imbalance. Many physicians feel that progesterone is safe in low doses (physiologic doses) in some breast cancer patients and may also be breast protective.

Progesterone is a natural hormone made by the adrenal glands and ovaries (and testes in men). Although progesterone and synthetic progestins both prevent proliferation of the uterine lining, they are very different compounds with very different effects in the body.

Progesterone is an integral part of the hormone balance and is a precursor hormone to Cortisol, aldosterone, estrogen, and testosterone. They synthetic progestins have been altered and minute differences in molecular structure convey vastly different biological messages.

Progesterone:

Necessary for the survival and development of the embryo
More quickly metabolized
Protects against fibrocystic breast tissues, may protect against breast cancer
Coronary (heart) vasodilator
Increases bone density and stimulates osteoblasts (cells that build bone)
Improves blood lipid profile
Natural diuretic
Natural antidepressant
Helps relieve headaches secondary to estrogen dominance
Normalizes blood glucose levels
Normalizes blood clotting
Increases sex hormone binding globulin, thus decreasing free estradiol
Burns fat for energy
Restores libido
Decreases the risk of ovarian and uterine cancers
Helps stimulate thyroid hormone action
Very claming hormone
Balances estrogen and testosterone
Brain protective
Non patentable

Progestins (Provera):

Increase the risk of early abortion and congenital deformities, it is used in the morning after pill
Metabolized more slowly causing side effects
May increase the risk of breast cancer
Constricts coronary vessels, negates the possibly protective effect of estrogen on the heart arteries
Not protective against osteoporosis, long term use can cause decreased bone density
Detrimental effects on lipids (cholesterol/triglycerides)
Fluid retention and edema
Can cause depression
Can cause migraine headaches
Decreases glucose tolerance
Increases thromobotic disorders (example: DVTs)
Decreases sex hormone binding globuling contributing to estrogen dominance
Causes weight gain
Decreases libido
Decreases the risk of ovarian and uterine cancers
Decreases thyroid action (decreases T3 uptake)
Increases anxiety and nervousness
Does not balance estrogen and testosterone and increases hirsutism
Increases the risk of dementia
Patentable = Profitable for pharmaceutical companies

Info from: Premier Women’s Health, Obstetrics and Gynecology

Our practice emphasizes disease prevention and health promotion, and we are trained to manage acute and chronic illnesses simultaneously. More important than ever, family practice physicians are needed to respond to the aging populations in need of quality health care.

Through coaching in lifestyle modification and the judicious use of medications we can improve your health and longevity. You are an active participant in this process. Together we will hasten your recovery from infectious diseases and your return to your highest level of functioning as we manage any chronic disease you may encounter.

As an informed patient, you’ll make better decisions concerning treatment options. The presented articles are to help you understand medical issues confronting Doctor’s today.

What your not being told about statin drugs.

I would like to call your attention to an additional report on statin adverse effects.

In a survey of 650 patients by Dr. Beatrice Golomb of the University of California at San Diego, 87% reported adverse drug reactions (ADR’s) to their doctors. Patients and not the doctors initiated the discussion in 98% of complaints involving cognition, 96% of those involving neuropathy, and 86% of those involving muscle complaints.
Physicians are far more likely to deny rather than affirm patient-reported ADR’s. Rejection by physicians occurred even when symptoms had strong literature-based support. Physicians are unlikely to report ADR’s to the Food and Drug Administration (FDA).

A continuing complaint from patients who report statin side effects is a lack of physician responsiveness and even actual hostility. Physician responses to a patient’s concerns that statins may be contributing to their memory loss, weakness, or depression vary from the imperious (“Satins don’t do that”) to the hostile (“Do what I say or get another doctor”) to the threatening (“If you do not do what I say, you are going to die”). There is no doubt that this reaction has greatly undermined patient-physician relationships and weakened respect for physicians’ authority.

I understand this reaction of front-line doctors, for I was there for 23 years. Direct-to-patient advertising has been a major contributor to this change in the patient-physician relationship, but there is another contributor, far more insidious: lack of doctor awareness of the true side-effect profile of our statin drugs. What we doctors know about a drug and its effects on the body is determined primarily by the pharmaceutical industry. Ever since the statin drugs were placed on the market (Merck’s lovastatin was the first) we have been told that we could expect some aches and pains and occasional liver inflammation that would respond to lowering of drug dose. For 20 years that is all we have been told. And this has been in a 40-year climate of perceiving cholesterol to be the enemy.

Meanwhile, victims of statin damage have dutifully submitted thousands of reports to Medwatch about their transient global amnesia, permanent peripheral neuropathy, permanent myopathy, chronic neuromuscular degeneration, and amyotrophic lateral scierosis-like condition, anxiously awaiting some response. I have waited 7 years for some reaction to my own two reports of Lipitor related amnesia, file with Medwatch. Now I find that none of this information is being transmitted back to the practicing physicians who write the prescriptions. When I enter their offices they are incredulous at my talk of amnesia episodes and permanent damage to muscle and nerves, including an ALS-Like syndrome.

I suggest that this current FDA and drug company philosophy of telling the doctors of our country only what they want them to know is the major contributor to the destruction of the patient-patient relationships. Our doctors have not been made aware of the truth, and soon will be targeted for legal action.

I wrote about this 5 years ago, and just this past month hundreds of mass tort cases have been filed in South Carolina for Lipitor/diabetes causation in women. As this becomes nationally known, there will soon be tens of thousands of cases.

Duane Graveline, M.D., M.P.H. of Merritt Island, Florida wrote this article in the winter of 2014

Healthy aging requires estrogen.

At the time of the Revolutionary War, only one American woman in twenty lived to the age of 50 (to experience menopause). The average life expectancy for women was 32.
In 1900, life expectancy had increased to 50.
Today, the average American woman lives to 84 years.

Less than 10% of women older than 70, are able to retain vigorous good health with hormone supplementation. Supplementing estrogen prevents 85% of osteoporosis.

In 2002, a study of 16,000 women taking Premarin and Progestin reported an increase risk of breast cancer. In 2007, these findings were reversed and actually found a 20% lower risk of breast cancer in users of estrogen.

Studies conducted over the past 15 years show that women who take estrogen have:

1. 37% reduction in hearth disease
2. 30% fewer bone fractures
3. 18% less breast cancer
4. 11% fewer strokes
5. 29% longer life

When women take progesterone with their estrogen, they decrease their risk of uterine cancer by approximately 20%.

Supplementing testosterone has been shown to enhance satisfaction in sex. Testosterone not only improves libido, but also supports good bone density, muscle tone, and decreases incidences of diabetes.

Women tend to blame estrogen for weight gain during menopause. Studies show that women who are not taking estrogen weigh about 8 pounds more after five years of menopause than those who took hormones.

When estrogen levels start to fall, there is a drop in the production of collagen and elastin within the inner layers of the skin. The thinner skin is more easily injured and may appear translucent or shiny.

Of hundreds of women tested in menopause, not one performed better without estrogen. The majority of women did at least 30% better in all areas of mental activity when they were using estrogen supplements.

Estrogen Supplements in older women is a “Quality of Life Issue”.

Prostate cancer is the most common noncutaneous cancer detected in American men and the second leading cause of cancer-related deaths. The incidence of prostate cancer increases with age. Where 30% of men aged
60-69 will have the disease; autopsy incidence increases to 67% in men age 80-89. A 50 year-old American man has a lifetime risk of 40% for latent cancer, 16% for developing clinically apparent cancer, and a 2.9 risk of death due to prostate cancer.
PSA testing increases the detection rate of prostate cancer. Approximately 2.5% of men older than 50 years of age will be found to have prostate cancer.
Two large, randomized trials question the benefit of screening men for prostate cancer. In the US Prostate Lung, Colorectal, and Ovarian (PLCO) Screening Trial, no mortality benefit was observed after combined screening with PSA testing and digital rectal examination during a follow-up of 13 years. Although screening resulted in a 12% increase in prostate cancer detection, the cancer-specific mortality rate was similar in the screening and control arms (3.7 and 3.4 deaths per 10,000 person-tears, respectively). Similarly in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial, the benefit of PSA screening was minimal with a 20% relative reduction in death rate at follow-up of 9 deaths per 10,000 men screened.
The United States Preventive Services Task recommendations may be accessed at http://www.ahrq.gov/clinic/pocketgd1011/gcp10s2.ht
These recommendations state:
1. There is insufficient evidence to recommend for or against screening
2. Screening is not recommended in men aged > 75.
Since incontinence of urine and impotence are potential side effects of the treatment, I personally do not recommend or receive prostate cancer screening.
I encourage you to do your own research and be assured I will follow your desire.

Androgen deficiency in aging men is a condition in which low levels of testosterone in an older man is associated with a decreased in sexual satisfaction or decline in a feeling of general well-being. Cross-sectional and longitudinal studies have demonstrated that testosterone levels at the rate of approximately 1% per year after the age of 30 years. Because of the increased of sex hormone-binding globulin (SHBG) levels with aging, there is an even greater decline in the free of bioavailable testosterone levels with aging.

The Pathophysiology Of Late-Onset Hypogonadism

In young men, the most common form of hypogonadism is testicular failure characterized by a decrease in testosterone and an increase in luteinizing (LH). In older people, testosterone levels decreases, but rarely to the level seen in primary hyogonadism in young men. The decrease is associated with only a small increase in LH, except late in life. The prevalence of hypogonadism has been estimated to be between 2% to 5% at 40 years of age and 30% to 70% by 70 years of age. It is estimated that at least 5 million men in the United States have hypogonadism, with less than 10% receiving hormone replacement.

The causes of late-life hypogonadism are multifactorial. Defects have been shown to occur at the level of gonadotrophin-releasing hormone (GnRH) pulse generator in the hypothalamus, the pituitary, and the testes. With aging, there is a decrease in Leydig cells and the testicular response to stimulation with human chorionic gonadotrophin. The negative feedback of testosterone at the pituitary level increases with aging. There is a decrease pulse generation of GnRH, with the pulses being generated more chaotically. It is the combination of these factors that leads to the age-related decline in testosterone level. In addition, with aging the normal circadian rhythm of testosterone secretion is lost.

Testosterone circulates in a free form and bound to albumin, and SHBG. In general, it is believed that the testosterone that is free and bound to albumin is available to tissues (bioavailable), whereas that bound to SHBG is not capable of entering tissues. With the aging, an increase in SHBG decreases the amount of bioavailable testosterone.

Biochemical Determination Of Testosterone

Many authorities believe that especially with the older person, free of bioavailable (albumin-bound + free) testosterone should be obtained.

Testosterone And Sexuality

In general, it is believed that the testosterone is a primary driver of libido. People with a low libido, generally have lower testosterone levels than those with a normal libido, but there is a marked overlap in testosterone levels in people with normal and abnormal libido. Hajjar and colleagues showed that testosterone replacement leads to a marked increase in libido. A meta-analysis has confirmed that testosterone increase enthusiasm for sex and sexual activity.

Testosterone levels are particularly low in people with diabetes mellitus and a low libido, and erectile dysfunction is commonly associated with diabetes.

Epidemiology

The prevalence of erectile dysfunction (ED) is difficult to estimate because of the assumed under reporting of the problem. Various age-dependent estimates have been made from population-based studies. Pinnock and colleagues reported that erections inadequate for intercourse affected 3% of men in their 40s, and increased to 64% of men in their 70s, based on an Australian community sample. In another Australian sample of consecutive male attendees to general medical practices, Chew and coworkers reported the prevalence of complete ED to be 2% of men in their 40s, and 50% of men in their 70s. Data on the incidence of ED form the Massachusetts Male Aging Study reported an increase from 12.4 cases per 1000 man-years for men in their 40s to 29.8 per 1000 man-years for men in their 50s, and 46.4 per 1000 man-years for men in their 60s.

Associations between serum testosterone levels and ED have not been clear in epidemiologic studies. Serum free-testosterone concentrations correlate with impaired relaxation of cavernous endothelial and corporeal smooth muscle in response to vasoactive challenge, independent of age. Factors that may be associated with both ED and low T levels include determinants of health (age, education, occupation, and ethnicity), behavioral and lifestyle (quality of life, alcohol intake, smoking, diet, and physical activity), clinical (diabetes, heart disease, hypertension, and drug therapies), and psychological factors, including depression and anxiety. There is a strong positive relationship between ED and cardiovascular risk factors and depression (the probability of ED is 90% in men who have severe depression, but only 25% in men who have mild depression). The causal relationship is unclear and possibly occurs through mechanisms involving reduced testosterone levels. A longitudinal study of the evolution of ED, associated factors, and comorbidities will provide this much needed data.

Prostate volume was not significantly related to circulating testosterone levels, but increase with increasing age and body mass index and decrease with increasing levels of SHBG in African Americans men. Neither elevated testosterone nor dihydrotestosterone predisposes men to BPH.

Biochemistry

In animal studies, androgen deprivation alters the functional responses and structure of erectile tissue. Penile tissue possesses high concentrations of locally synthesized androgens and thus androgen-dependent functions need not reflect circulating androgen levels. It is well documented in rats that testosterone is required for adequate function of nitric oxide synthase, which produces nitric oxide necessary for relaxation of cavernosal endothelial and corporeal smooth muscle resulting in erection.

Intervention

In the absence of significant hypogonadism, testosterone treatment does not have an effect on erectile function but it does improve the response to Viagra. Aversa and colleagues showed that in men who had erectile dysfunction, low free testosterone levels, independent of age, correlated with impaired relaxation of cavernous endothelial and corporeal smooth muscle cells. Moreover, a follow-up study in men who had arteriogenic erectile dysfunction, testosterone levels in the lower quartile of the normal range, and who were nonresponsive to Viagra treatment after six attempts, demonstrated that one month of transdermal testosterone supplementation improved erectile response to Viagra. Several studies have suggested enhanced strength or maintenance of erections following testosterone replacement in older men.

Furthermore, a meta-analysis of the usefulness of androgen replacement for erectile dysfunction showed that testosterone-treated patients improved significantly more that placebo-treated patients and those patients with primary testicular failure responded better to treatment than those with secondary testicular failure.

Skeletal Muscle Mass And Strength

Epidemiology

Muscle mass decreases and fat mass increases with increasing age. In the New Mexico Ageing Process Study, the best predictor of loss of muscle and strength (sarcopenia) was free testosterone. Other predictors include age, caloric intake, physical activity, and insulin like growth factor – (IGF) 1. Sarcopenia leads to frailty, an important precursor of subsequent functional deterioration and death. Frailty has been defined objectively by the criteria of weight loss, exhaustion, weakness (grip strength), slow walking speed, and low physical activity. Several hormones are believed to play a role in the pathophysiology of frailty. People who have diabetes mellitus are at high risk for developing premature frailty. Weight loss, which can be because of sarcopenia, anorexia, cachexia, or dehydration, is a hallmark of frailty. In men, obesity, particularly when the fat is distributed within the abdomen (visceral), is associated with low plasma testosterone. Conversely, decreased testosterone levels in men are associated with increased accumulation of visceral fat and are reversible on testosterone administration.

Van de Beld and coworkers are reported inverse cross-sectional associations between total, free, and bioavailable testosterone and total fat mass in 403 community-dwelling men aged 73 to 94 years. Moreover, both total and bioavailable testosterone were positively associated with handgrip strength. Denti and colleagues showed an age-independent, inverse association between SHBG and whole body fat percentage estimated from four skinfold measurements using the Durin-Wormsely and Siri equations in 206 healthy volunteers aged 18 to 95 years. In a longitudinal study it was shown that people who have lost muscle mass but remain obese (sarcopenic obesity) have an extremely high rate of future disability and death. It has been shown that sarcopenia is strongly related to the loss of hormones, such as testosterone and IGF-1, and to mild increases in cytokines, such as TNF-a and IL-6. Other causes of sarcopenia include diminished neuronal input to muscle, decreased food intake (particularly protein and creatine), and peripheral vascular disease.

Low levels of gonadal steroids and changes in the activity of the IGF axis therefore may be markers of the metabolic syndrome associated with increasing age, visceral obesity, impaired glucose tolerance and insulin signaling, and cardiovascular disease, resulting in accelerated frailty and death.

Biochemistry

Changes in the IGF/insulin signaling pathway with aging are likely to play a central role in regulation of skeletal muscle mass. Skeletal muscle is responsible for the production of 25% of circulating IGF-1. There are two muscle isoforms, one similar to liver IGF-1 and the other (IGF-IEc) mechanogrowth factor (MGF-1), having local actions on muscle. Exercise (stretch) leads up to regulation of the mRNA for both muscle isoforms and reduced muscle IGF-1 signaling leads to muscle atrophy. Hormones (growth hormone, testosterone, insulin, and vitamin D) and exercise regulate muscle IGF-1. It is the decline in the muscle isoforms of IGF-1 (liver like and MGF) that are likely to contribute most to age-related sarcopenia. Moreover, age-related decline in testosterone and growth hormone may lead to increase myostatin expression and dissociation in IGF-1 autocrine effects on protein synthesis in skeletal muscle.

The mechanisms by which testosterone, growth hormone, IGF-1, and other growth factors interact with receptor activity, myostatin gene expression, and satellite cell function in aged skeletal muscle to influence muscle protein warrant further vigorous research.

Intervention

Testosterone replacement in young hypogonadal men and supraphysiologic treatment in eugonadal young men have shown to increase muscle mass and strength. In older men who have low bioavailable testosterone or low-normal total testosterone level, intramuscular testosterone increases muscle mass and strength. In the study by Wittert and colleagues it was shown that change in lean mass correlated with change in quadriceps strength from baseline to month 12 in the testosterone but not in the placebo group. Urban and coworkers reported that intramuscular testosterone increases muscle IGF-1 and mRNA. Snyder and colleagues reported an increase in serum IGF-1 in men receiving testosterone by transdermal patch. Bhasin and coworkers have shown that the muscle response to testosterone in young men in relation to dose. The use of muscle function testing in the elderly is confounded by wide variability in most measures. Motivation, tolerance to pain, and potential learning effects may be some of the major factors limiting the ability of these tests to identify differences between the treatment groups in interventional studies. Accordingly, large study groups may be required to determine small treatment benefits.

Testosterone And Bone

Men fracture their hips approximately 10 years later than women do. Men have a higher mortality rate than women when they fracture their hips. Minimal trauma hip fracture is associated with low testosterone levels. The relationship of testosterone to bone is less clear in men. Several studies have shown that testosterone treatment can increase bone mineral density. The 5-alpha-reductase inhibitor does not block this effect of testosterone. It would seem that aromatization of testosterone to estrogen is the major cause of the positive effects of testosterone on bone. This effect has been demonstrated clearly in people with congenital aromatase deficiency. Testosterone also seems to have direct effects on the osteoblast.

Testosterone And Cognition

Low bioavailable testosterone levels are correlated with poor cognition, especially visual-spatial cognition. Some studies have demonstrated that testosterone replacement may improve visual-spatial cognition.

The SAMP8 mouse has poor cognition, which is attributable to overproduction of amyloid-beta protein associated with increased oxidative damage. The SAMP8 mouse has low testosterone levels. Testosterone replacement in this mouse model of Alzheimer disease improves learning and memory. Testosterone treatment decreases amyloid precursor protein.

Low testosterone levels are associated with an increased likelihood of developing Alzheimer disease. Patients with Alzheimer disease have low testosterone levels in brain tissue compared with controls. Testosterone replacement has been shown to produce small improvements in cognition in people who have Alzheimer disease.

Testosterone And Health-Related Quality Of Life

Heath relates quality of life (HRQOL) is a complex and abstract concept that includes physical, psychological, social, and other domains of functioning specific to a given health condition. It focuses on the ways n which a disease modifies the happiness and satisfaction of an individual. It represents the patient’s viewpoint of the effects of treatment. It generally has several domains, including symptoms, function, emotional stability, social functioning, and general satisfaction with life. In the case of hypogonadism, decreased energy levels and impaired sexual performance appear to be to be the most important quality-of-life areas. Lowering testosterone levels in patients who have prostate cancer results in deterioration in the HRQOL.

Diagnosis Of Hypogonadism In Older Men

The diagnosis of hypogonadism in older men requires the presence of a constellation of signs and symptoms, and a demonstrated low total testosterone or preferably, free or bioavailable testosterone level. Several questionnaires have been developed to help screen for andropause and to provide an objective measure of treatment response. Two of these have excellent specificity: the Saint Louis University ADAM questionnaire and the Aging Male Survey. Unfortunately, neither questionnaire has very good sensitivity. Because of the multiple causes of symptoms similar to the male hypogonadism in older men, it is unlikely that any questionnaire will perform much better.

A simplified algorithmic approach to diagnosing late-life hypogonadism is presented below. This approach is compatible with recent consensus recommendations.

A positive screen for hypogonadism includes a “Yes” response to numbers 1 and 7, or any other 3 questions.

1. Do you have a decreased in libido (sex drive)?
2. Do you have a lack of energy?
3. Do you have a decrease in strength and/or endurance?
4. Have you lost height?
5. Have you noticed a decreased enjoyment of life?
6. Are you sad and/or grumpy?
7. Are your erections less strong?
8. Have you noticed a recent deterioration in your ability to play sports?
9. Are you falling asleep after dinner?
10. Has there been a recent deterioration in your work performance?

Testosterone Treatments

Several different methods of testosterone treatments have been developed. Testosterone can be given as injections every 1 to 3 weeks. The major problem with this approach is that the levels of testosterone vary from supraphysiologic to low over each treatment period. This approach has been used successfully, however, for more than 70 years. A long-acting testosterone undecanoate injection has been developed in Asia and Europe and should be available in the United States next year. This treatment is similar to testosterone pellet implant therapy, which can be implanted every 4 to 6 months.

Testosterone patches have a high rate of skin irritation because of alcohol being a part of the vehicle. Hydroalcoholic gels containing 1% testosterone have become popular in the United States. They have a lower rate of skin irritation and a better patient acceptance. Doses vary from 50 to 100 mg of gel daily. Three-year safety data fro this form of treatment have been reported. This study showed continued positive results of treatment on muscle, bone, fat, and libido in men age 19 to 67 years. Two forms of testosterone gel, AndroGel and Testim, are available in the United States.

Testosterone And The Cardiovascular System

Low testosterone levels are correlated with increased atherosclerosis and an increased carotid-intima media thickness. Testosterone decreases angina and decreases ST depression. It has minimal effects on cholesterol. Testosterone improves walking speed in peoples with congestive heart failure. Overall, these small studies suggest a beneficial effect of testosterone on heart disease.

Side Effects

The major side effect of testosterone is an excessive increase in hematocrit. When the hematocrit increases to more than 55, testosterone therapy should be withheld. Testosterone also can be associated with worsening sleep apnea. Testosterone therapy can be associated with the development of gynecomastia related to the aromatization of testosterone to estrogen. Parenteral testosterone administration has minimal deleterious effects on the liver.

Summary

Testosterone deficiency occurs commonly in men, as they grow older. This deficiency often is associated with a decline in sexual activity and a loss of muscle mass. Testosterone replacement can reverse many of these effects. At present, no ideal form of testosterone replacement is available.

Testosterone Replacement in older men is a “Quality of Life Issue”.

The Stanford Hospital Health Library is a valuable source for patients to gain up-to-date medical information which is unbiased. You can also visit the Stanford Health Library’s web site at: healthlibrary.stanford.edu

Or call 1-800-295-5177 and a librarian will answer. Ask what you want to know, for example, “Is Lipitor safe for lowering my cholesterol?” The librarian will research the literature and send you information via mail. There is no charge for this service. Their e-mail address is: healthlibrary@stanfordmed.org