In part one of this series we looked at the cause of polycystic ovarian syndrome (PCOS) and the many complications it causes. Weight gain, acne, excess hair growth on the face and body, high cholesterol and high blood sugar due to insulin resistance are among the problems associated with PCOS. One particular area of concern for PCOS sufferers is infertility due to lack of ovulation. PCOS is the cause of anovulatory infertility in 3 out of 4 cases. Before the acceptance of medical therapy for infertility due to PCOS a surgical approach referred to as a wedge resection of the ovary was performed which allowed patients with PCOS to ovulate and conceive normally. Low success rates with this procedure, complications of surgery and improved medical therapies have all resulted in the end of this type of treatment in most situations. At present, treatment of infertility associated with PCOS generally consists of using a drug to combat insulin resistance known as metformin often in combination with the fertility drug clomid, which has a high rate of success.
Treatment of the excess hair growth associated with PCOS often consists of using the drug spironalactone and the use of birth control pills. Spironalactone is a very interesting drug used for decades as a salt depleting diuretic but also has an effect to block the action of the male hormone testosterone. The action of spironalactone to block testosterone was discovered when it was noticed that men using this diuretic developed tender nipples and breast enlargement (gynecomastia). Oral contraceptive agents are also useful to combat hirsutism because these agents also cause reduce testosterone levels by putting the ovary in a dormant “resting” state. Cosmetic procedures are always another option to treat unwanted hair growth. Laser hair removal appears to be replacing the older modality of electrolysis for this purpose.
Can PCOS be cured? Once PCOS develops it can be controlled but not cured unless the ovaries are removed. At menopause PCOS-related problems diminish as the ovary stops making sex hormones including testosterone which is one of the culprits during the reproductive years. A recent study published this year in the journal Pediatric Endocrinology showed that using metformin treatment in pre-adolescent girls thought to be at risk for PCOS reduces the risk and/or the severity of PCOS in later years. It may do this by blocking fat accumulation in the abdomen and liver which seems to set off the insulin resistance. Metformin is not FDA approved for this purpose and as a generic drug there is little profit potential in developing this treatment. I expect it will be many years before preventive therapy for PCOS will come before the FDA for approval .
This information is strictly for educational purposes. Due to high risk of toxicity of medical therapy in young women who can potentially become fertile under treatment for PCOS, no drug should be taken without the close supervision of a physician. The reader agrees to the Terms of Service of this website, metabolism.com
When I became an endocrinologist in 1981 I was truly excited about the field. At that time it seemed that the science of endocrinology was expanding rapidly and new discoveries were on the horizon particularly in regards to the way hormones effect the brain, mood and the immune system. Was I ever wrong! It’s thirty years later and none of those expectations were realized. In fact, I find that the field of endocrinology has barely budged since then and in some areas has actually lost ground.
Bringing on this round of pessimism on my part, is a recent “development†in the area of treatment for hyperthyroidism (over active thyroid). Ever since I was in training there have been two medicines, propylthiouracil (PTU) and methimazole (Tapazole), which are the mainstays of medical treatment for hyperthyroidism. Both medicines have been available since the 1940’s and show excellent efficacy and tolerability (and they are cheap!). Almost all endocrinologists I have met use these two drugs interchangeably although in pregnancy propylthyiouracil is favored due to rare birth defects in fetuses exposed to methimazole.
The “development†which I find so discouraging is the recent action by the FDA to place a very strict (black box) warning on the use of PTU due to the possible occurrence of a rare form of liver injury attributed to the drug. After almost 70 years of exemplary use, this has given rise to extensive debate in the endocrinology literature about how to restrict PTU use.
While it is true that methimazole is equally as effective as PTU to treat hyperthyroidism, I have personally seen numerous cases of fairly severe allergic reactions to methimazole. Fortunately it has been easy to continue medical treatment by simply switching to PTU. If we can’t use PTU freely then the only other options are surgical removal of the thyroid or eradication of the thyroid using radioactive iodine, neither of which is free of potentially adverse outcomes.
I have never encountered severe liver injury with PTU nor has any of the colleagues I have polled. It has to be very, very rare. This is obvious because it has taken 70 years to get around to recognizing it formally. Can we really call it progress that we now have one less simple option for treating hyperthyroidism, a common and relatively benign disease? Let me take my cynicism to the next level. I won’t be surprised if a major pharmaceutical company soon announces the development of a new drug for treating hyperthyroidism. If I’m right the new drug will add nothing of real value that wasn’t previously available but is many times more expensive then the drug it replaces.
So goes endocrinology into the new century, the stogy old lady of medicine.
Puberty occurs when areas within the brain awaken beginning a cascade of hormone signals which conclude with the gonads (ovaries and testicles) increasing their production of the female and male sex hormones estrogen and testosterone. Under the influence of these hormones a child begins the transition from childhood to sexual maturity. In boys puberty is associated with a growth spurt, the appearance of facial, axillary (arm pit) and pubic hair, acne, deepening of the voice, growth of the testicles and penis while girls undergo a growth spurt, develop breasts, acne, pubic and axillary hair, and growth of the clitoris.
Historical data shows the average age of puberty today is many years sooner than in previous generations. Most experts attribute earlier puberty to better nutrition. A recent article in metabolism.com reviewed how “over-nutrition” accelerates obese children into puberty sooner (referred to as precocious puberty) than normal weight children. The latest studies on causes of precocious puberty suggests that a child’s social environment also exerts an important influence on the timing of puberty. Researchers in Madrid publishing in The Journal of Clinical Endocrinology and Metabolism 95:4305 2010 analyzed the age of puberty in normal children, adopted children and children whose families immigrated (children not adopted but subject to high levels of personal stress) to Spain. Adopted children were 25 times more likely than other groups of children to undergo precocious puberty (breast development before the age of 8 years in girls, and boys under 9 years of age with testicular growth). Over-all girls were 11 times more likely than boys to demonstrate precocious puberty.
Researchers speculate that socio-emotional stresses early in life of children who are later adopted result in changes in the brain that cause premature maturation of vital nerve pathways. This early brain maturation later results in stimulation of the pituitary gland, turning on the hormone pathways that cause puberty. This seems strange to me because various forms of deprivation in childhood can also delay puberty. For example, girls who have anorexia remain child-like in their body development and may fail to menstruate even into their late teens. A decade ago I studied hormone levels in adults during the stress of illness and surgery and found this lowered the sex hormone levels in their blood. This makes sense from an evolutionary point of view because during stressful conditions nature wisely cuts off the reproductive hormones. Why make babies if the environment is hostile in some way? Why the opposite occurs in children under stress of adoption is an interesting but unanswered question.
Gary Pepper, M.D.,
Editor-in-Chief, metabolism.com
It seems obvious that cutting away part of the stomach and intestine should cause weight loss. With a smaller stomach and less intestine fewer calories can be absorbed per day causing weight loss. Surgeons who perform gastric by-pass were puzzled however, by how fast their patients showed metabolic improvement after undergoing this procedure. They noticed many of their diabetic patients could be taken off diabetic medication immediately after surgery before weight had been lost. Scientists looking into this phenomena discovered unsuspected ways gastric by-pass improved metabolism.
The intestines produce hormones which regulate blood sugar and appetite. GLP-1 is among the best known of these intestinal hormones. GLP-1 is the basis of a whole new generation of medications used to treat diabetes such as Byetta, Victoza, Januvia and Onglyza. GLP-1 lowers blood sugar, stimulates the pancreas and reduces appetite. After gastric by-pass increased amounts of GLP-1 are produced by the remaining intestine. In a study published in the Journal of Clinical Endocrinology and Metabolism (95:4072-4076, 2010), researchers at St. Luke’s Hospital in New York discovered that levels of oxyntomodulin, another intestinal hormone that suppresses appetite and acts like GLP-1 on blood sugar levels, is doubled after gastric by-pass.
These exciting discoveries help explain why obese diabetics can often be sent home without any medication to control blood sugar immediately after undergoing gastric by-pass surgery. Although most insurance plans do not cover gastric by-pass surgery, dramatic improvements in patients after the procedure with greatly reduced medication costs may convince insurance companies that paying for the procedure will result in better outcomes and save them money in the long run.
Due to the potential for abuse and high cost, growth hormone treatment in adults is the subject of much controversy. I believe that treating adults with growth hormone deficiency is many times an appropriate and beneficial choice. Firming up my conviction for treating adult growth hormone deficiency is a recent study conducted in the Netherlands and UK published in the Journal of Endocrinology and Metabolism (JCEM 95:3664-3674, 2010). The researchers compared Body Mass Index (BMI), waist circumference, triglycerides, and HDL (good cholesterol), between normal adults and those with low growth hormone levels due to deficient pituitary function (hypopituitarism). All measurements of obesity and lipid metabolism were significantly worse in the young adults (younger than 57 years) with growth hormone deficiency compared to normal adults of a similar age.
As I pointed out in previous articles at metabolism.com, growth hormone levels naturally decline as we get older. The authors of the present study note that growth hormone levels decline 14% per decade in adults. I conceive of this as one of the ways nature gets rid of us after we complete our biological/reproductive functions, since without growth hormone our muscles, immune and nervous systems, decline, leading to death. It’s planned obsolescence… what is typically referred to as aging. In the recent study senior citizens have equivalent levels of obesity and abnormal lipid metabolism as young adults with growth hormone deficiency. The authors note the effect on the body of growth hormone deficiency in young adults is equivalent to 40 years of aging. The theory that growth hormone functions to preserve our tissues during youth and aging results from its absence, appears confirmed by these results.
Most normal young adults aren’t growth hormone deficient and the population that would qualify for growth hormone treatment from this group is small. What about older adults with low growth hormone who are troubled by the “natural†decline in their body function? Should or could we treat this much larger population with growth hormone? It is my experience that private and federal insurers will not pay for this treatment regarded as “cosmeticâ€. On the other hand, there will be physicians who will comply with a request for growth hormone treatment from individuals who possess enough cash and motivation. Less affluent or determined individuals will have to contend with natural aging just as our ancestors have done for thousands of years.
This information is for educational purposes only and is not intended as medical advice or treatment.
Gary Pepper, M.D.
Editor-in-Chief, metabolism.com.
The mission of the The Thyroid Project is to encourage sharing of information and experience between the public and the medical community about the treatment of hypothyroidism (low thyroid function). For at least the past few decades there is a growing awareness of “something missing†in the way suffers of hypothyroidism are treated for their disease.
Too many patients, as documented in an on-line study of 12,000 individuals conducted by the American Thyroid Association published in June 2018, (https://doi.org/10.1089/thy.2017.0681) , complain of persistent symptoms of hypothyroidism despite what their doctors believe is successful treatment with levothyroxine (brands include Synthroid, Unithroid, Tirosent, Levoxl). We believe something needs to be done to resolve this conflict between patients and their doctors.
Without effective intervention the early stage of type 2 diabetes known as prediabetes carries a high risk of progressing to outright diabetes. Metabolism.com provides an up-to-date summary of recommendations from national authorities, for preventing and possibly reversing this life long affliction
Diabetes can be defined simply as elevated blood sugar levels. What exactly is high blood sugar and when should someone be concerned about their level? Does having prediabetes mean diabetes is around the corner? Metabolism.com tackles this tricky but important topic in this comprehensive review.
By Gary M. Pepper, M.D. Ozempic, Rybelsus, Trulicity, Wegovy, Saxenda are the central players in the weight loss craze sweeping across the globe. Metabolisim.com has been monitoring this phenomenon from its beginnings in 2008 with its report “Lizard Spit Reduces Blood Sugar and Appetite”, regarding the first drug in this class, Byetta (exenatide). Caught In the middle of the current chaos are the medical experts who treat diabetes and have been prescribing these medications for more than a decade. Here is a brief commentary from one such board certified endocrinologist; “I started treating Type 2 diabetics with GLP-1 agonists more than 10 years ago. In some respects, these medications have revolutionized the treatment of diabetes by lowering blood sugar effectively and promoting weight loss at the same time, a unique combination of benefits. Not everyone benefits from these drugs to the same degree unfortunately, and I have seen lots of patients experience unacceptable side effects from them. Nothing though, has prepared me for what is happening now. Too often, I find myself confronting someone who expects me to prescribe one of these drugs just so they can lose weight. Sadly, one extreme example was someone who, despite battling a life threatening medical condition, was insistent on getting a prescription. At the same time my diabetic patients are scrambling to find a place to buy their medications if they can even afford it. It is disheartening, to say the least, and I dread the negative interactions with some of my patients I now face almost daily.”
Off- Label Use
The FDA is the U.S. government’s department tasked with evaluating and approving drugs for specific medical conditions. When a new medication is approved for treating a medical condition by the FDA the agency will, at the same time, set strict guidelines for exactly which patients may use the newly approved drug. When a medication is used “off-label” it means that these limitations are being overridden by the provider for a potential benefit which outweighs the drugs risks. It is a general misconception that off-label means illegal; it does not. This practice has been going on for ages and more than 20% of prescriptions in the United States are prescribed off-label. A common example is the use of beta-blockers (approved for heart problems) for the treatment of performance anxiety.
GLP-1 agonist drugs, as discussed recently by metabolism.com. were originally approved for the treatment of Type 2 diabetes in adults. In the past few years most of these same medications have gained unprecedented popularity for their “off-label” weight loss benefit. Of the 5 GLP-1 agents presently in U.S. pharmacies only Wegovy (semaglutide) and Saxenda (liraglutide) are FDA approved for treating obesity. Of these two, Wegovy is the newer and had been much more popular that its sister drug Saxenda, probably due to being dosed only once weekly compared to daily for Saxenda and less likely to cause side effects. Due to Wegovy’s soaring popularity, its manufacturer, Novo Nordisk, increased the price of Wegovy two times since its initial release.
In part one of this series we looked at the cause of polycystic ovarian syndrome (PCOS) and the many complications it causes. Weight gain, acne, excess hair growth on the face and body, high cholesterol and high blood sugar due to insulin resistance are among the problems associated with PCOS. One particular area of concern for PCOS sufferers is infertility due to lack of ovulation. PCOS is the cause of anovulatory infertility in 3 out of 4 cases. Before the acceptance of medical therapy for infertility due to PCOS a surgical approach referred to as a wedge resection of the ovary was performed which allowed patients with PCOS to ovulate and conceive normally. Low success rates with this procedure, complications of surgery and improved medical therapies have all resulted in the end of this type of treatment in most situations. At present, treatment of infertility associated with PCOS generally consists of using a drug to combat insulin resistance known as metformin often in combination with the fertility drug clomid, which has a high rate of success.
