Nelson Vergel's Blog, page 6

Depressive Symptoms and Suicidal Thoughts Among Former Users of Finasteride (Propecia, Proscar) With Persistent Sexual Side Effects

Michael S. Irwig, MDJ Clin Psychiatry10.4088/JCP.12m07887Copyright 2012 Physicians Postgraduate Press, Inc.




Objective: Finasteride, a commonly prescribed medication for male pattern hair loss, has recently been associated with persistent sexual side effects. In addition, depression has recently been added to the product labeling of Propecia (finasteride 1 mg). Finasteride reduces the levels of several neuroactive steroids linked to sexual function and depression. This study assesses depressive symptoms and suicidal thoughts in former users of finasteride who developed persistent sexual side effects despite the discontinuation of finasteride.
Method: In 2010–2011, former users of finasteride (n = 61) with persistent sexual side effects for ≥ 3 months were administered standardized interviews that gathered demographic information, medical and psychiatric histories, and information on medication use, sexual function, and alcohol consumption. All former users were otherwise healthy men with no baseline sexual dysfunction, chronic medical conditions, current or past psychiatric conditions, or use of oral prescription medications before or during finasteride use. A control group of men (n = 29), recruited from the community, had male pattern hair loss but had never used finasteride and denied any history of psychiatric conditions or use of psychiatric medications. The primary outcomes were the prevalence of depressive symptoms and the prevalence of suicidal thoughts as determined by the Beck Depression Inventory II (BDI-II); all subjects self-administered this questionnaire at the time of the interview or up to 10 months later.
Results: Rates of depressive symptoms (BDI-II score ≥ 14) were significantly higher in the former finasteride users (75%; 46/61) as compared to the controls (10%; 3/29) (P < .0001). Moderate or severe depressive symptoms (BDI-II score ≥ 20) were present in 64% (39/61) of the finasteride group and 0% of the controls. Suicidal thoughts were present in 44% (27/61) of the former finasteride users and in 3% (1/29) of the controls (P < .0001).
Conclusions: Clinicians and potential users of finasteride should be aware of the potential risk of depressive symptoms and suicidal thoughts. The preliminary findings of this study warrant further research with controlled studies.J Clin Psychiatry


Source: http://article.psychiatrist.com/dao_1-login.asp?ID=10007988&RSID=31923221437757

Study Looked at What Happens When Long Term Growth Hormone Replacement Therapy is Stopped

Discontinuing Long-Term GH Replacement Therapy—A Randomized, Placebo-Controlled Crossover Trial in Adult GH DeficiencyHelena Filipsson Nyström, Edna J. L. Barbosa, Anna G. Nilsson, Lise-Lott Norrman,Oskar Ragnarsson and Gudmundur Johannsson-Author AffiliationsAbstractContext: Adult GH deficiency (GHD) is associated with impaired quality of life (QoL) and increased cardiovascular risk. Continued long-term efficacy in terms of QoL and cardiovascular risk factors has been indicated in open surveillance studies.Objectives: The aim was to study the impact of discontinuation of long-term GH replacement on QoL, body composition, and metabolism.Design and Setting: We conducted a randomized, double-blind, placebo-controlled 4-month crossover trial in a referral center.Patients: Sixty adult hypopituitary patients with GHD and more than 3 yr of continuous GH replacement therapy (mean treatment duration, 10 yr) participated in the study.Intervention: Patients received GH or placebo.Main Outcome Measurements: We measured QoL using validated questionnaires; body composition using computer tomography, dual-energy x-ray absorptiometry, and bioelectrical impedance spectroscopy; and insulin sensitivity using the short insulin tolerance test.Results: Mean serum IGF-I decreased from 168± 52 to 98± 47 µg/liter during the placebo period (P< 0.001). Two QoL domains (emotional reactions and positive well-being) in the Nottingham Health Profile and Psychological General Well-Being questionnaires deteriorated during placebo, compared with GH treatment (P< 0.05). Waist circumference and sc and visceral fat mass increased, and extracellular water and muscle area decreased during the placebo period (all P< 0.05). C-reactive protein and total-, low-density lipoprotein-, and high-density lipoprotein-cholesterol increased, and insulin sensitivity improved during placebo, compared to GH treatment (P< 0.05).Conclusion: After more than 3 yr of GH replacement therapy, a 4-month period of placebo treatment caused self-perceived deterioration in QoL and increased abdominal fat accumulation. Moreover, markers of systemic inflammation and lipid status deteriorated, whereas insulin sensitivity improved. Long-term continuous GH replacement is needed to maintain therapeutic effects of GH on QoL and cardiovascular risk factors.

HCG Use in Men

Human Chorionic Gonadotropin




Excerpt from the book “Testosterone: A Man’s Guide” by Nelson Vergel (available on Amazon.com or in different formats on TestosteroneWisdom.com). NelsonVergel@gmail.com

Human chorionic gonadotropin (HCG) (not to be confused with human growth hormone, or HGH) is a glycoprotein hormone that mimics LH (luteinizing hormone), produced in pregnancy by the developing embryo soon after conception, and later by part of the placenta. Its role is to prevent the disintegration of the corpus luteum of the ovary and to maintain the progesterone production critical for pregnancy in women. It supports the normal development of an egg in a woman’s ovary, and stimulates the release of the egg during ovulation. HCG is used to cause ovulation and to treat infertility in women.
HCG is also used in young boys when their testicles have not dropped down into the scrotum normally.  Additionally, HCG is used to increase testicular size after long-term testosterone or anabolic steroid use. However, the latter is an off-label use.
Testosterone replacement therapy triggers the hypothalamus to shut down its production of GnRH (gonadotropin releasing hormone). Without GnRH, the pituitary gland stops releasing LH. Without LH the testes (testicles or gonads) shut down their production of testosterone. For males HCG closely resembles LH. If the testicles have shrunken after long-term testosterone use, they will likely begin to enlarge and start their testosterone production shortly after HCG therapy is instituted. HCG jump-starts your testes to produce testosterone and to increase their size.
HCG can be extracted from pregnant women’s urine or through genetic modification. The product is available by prescription under the brand names Pregnyl, Follutein, Profasi, and Novarel. Novire is another brand but it is a product of recombinant DNA. Compounding pharmacies can also make HCG by prescription in different vial sizes. Brand names of HCG in regular pharmacies cost over $100 per 10,000 IUs.  The same amount of IUs cost around $50 in compounding pharmacies. Many insurance policies do not pay for HCG since they consider its use for testicular atrophy while on TRT an off label use. So, most men using it pay for it themselves and get it from compounding pharmacies that sell it a lot cheaper.
HCG is dispensed as a powder contained in vials of 3,500 IUs, 5, 000 IUs or 10, 000 IUs (depending on the compounding pharmacy, these amounts may vary). You can call compounding pharmacies and have them make vials for you with different IU amounts, though. These are usually accompanied by another vial of 1 mL (or cc) of bacteriostatic water to reconstitute the powder into a liquid solution. Bacteriostatic water (water with a preservative that is provided with the prescription) is mixed in with the powder to reconstitute, or dissolve, it before injection. This type of water can preserve the solution for up to 6 weeks when refrigerated. Some patients do not use the 1 mL water vials that come with the commercially (non compounded) available product and instead get their doctors to prescribe 30 cc bottles of bacteriostatic water so that they can dilute the HCG down to a more workable concentration that is more practical for men using lower doses of HCG weekly.
HCG is given as an injection under the skin or intramuscularly (there is still debate on which method is best). The number of IUs per injection will depend on how much bacteriostatic water you add to the dry powder vial. If you add 1 mL to a 5,000 IU powder vial, then you will have 5,000 IUs per mL, so 0.1 mL would be 500 IUs. If you add 2 mL to the 5,000 IU dry powder vial, then you will have 2,500 IUs/mL; 0.1 ml (or cc) in an insulin syringe will equal 250 IUs. If you need to inject 500 IUs, then you inject 0.2 ccs of this mixture. Table 3 provides dilution volumes at different HCG powder/water proportions.
Ultra-fine needle insulin syringes are used to inject HCG under the skin, making this very easy to take even for the needle-phobic. Typical sizes are:
•          1 ml, 12.7 mm long, 30 gauge and•          0.5 ml, 8 mm, 31 gauge syringes.
Syringes require a separate prescription. Some compounding pharmacies will automatically include them with the shipment, but do not forget to ask them. Never use the syringe that you used for injecting the bacteriostatic water into the powder for injecting yourself; the needle will be dull (I usually use a regular 23 gauge, 1 inch, 3 ml syringe to load up the water). Remember that you also need alcohol pads to clean the injection area and the tip of the vial. Typical injection sites are the abdominal area close to the navel or in the pubic fat pad. Pinch a little of fat on your abdominals and inject into that pinched area, then massage with an alcohol pad. Discard syringes into the sharps container that can be provided by your pharmacy.
As I mentioned before, compounded HCG is a lot cheaper than the commercially available pharmaceutical products. Also, it is sometimes difficult to find commercially available HCG in regular pharmacies.
A review of the literature reveals a wide range of doses of HCG used and that there is very little agreement among physicians. For male infertility, doses range from 1250 IU three times weekly to 3000 IU twice weekly (these studies did not include men on testosterone replacement).
How long does the boost in testosterone last after an injection of HCG? A study looked into that and also tried to determine if high doses would be more effective at sustaining that boost. The profiles of plasma testosterone and HCG in normal adult men were studied after the administration of 6000 IU HCG under two different protocols. In the first protocol, seven subjects received a single intramuscular injection. Plasma testosterone increased sharply (1.6 ± 0.1-fold) within 4 hours. Then testosterone decreased slightly and remained at a plateau level for at least 24 hours. A delayed peak of testosterone (2.4 ± 0.3-fold) was seen between 72–96 hours. Thereafter, testosterone declined and reached the initial levels at 144 hours. In the second protocol, six subjects received two intravenous (IV) injections of HCG (5-8 times the dose given by injection to the first group) at 24-hour intervals. The initial increment of plasma testosterone after the first injection was similar to that seen in the first protocol despite the fact that plasma HCG levels were 5–8 times higher in this case. At 24 hours, testosterone levels were again lower than those observed at 2–4 hours and a second IV injection of HCG did not induce a significant increase. The delayed peak of plasma testosterone (2.2 ± 0.2-fold of control) was seen about 24 hour later than that in the first protocol. So, this study shows that more is not better when dosing HCG. In fact, high doses may desensitize Leydig cells in the testicles.  It also showed that testosterone blood levels peak not once but twice after HCG injections.  I wish they had studied a lower dose than 6000 IU since very few physicians prescribe this high dose.
HCG may not only boost testosterone but also increase the number of Leydig cells in the testicles. It is well known that Leydig cell clusters in adult testes enlarge considerably under treatment with HCG. However, it has been uncertain in the past whether this expansion involves an increase in the number of Leydig cells or merely an enlargement of the individual cells. A study was performed in which adult male Sprague-Dawley rats were injected subcutaneously daily with 100 IU HCG for up to 5 weeks. The volume of Leydig cell clusters increased by a factor of 4.7 during the 5 weeks of HCG treatment. The number of Leydig cells (initially averaging 18.6 x 106/cm3 testis) increased to 3 times the control value by 5 weeks of treatment.
Currently there are no HCG guidelines for men who need to be on testosterone replacement therapy and want to maintain normal testicular size. A study that used 200 mg per week of testosterone enanthate injections with HCG at doses of 125, 250, or 500 IU every other day in healthy younger men showed that the 250 IU dose every other day preserved normal testicular function (no testicular size measurements were taken, however). Whether this dose is effective in older men is yet to be proven. Also, there are no long-term studies using HCG for more than 2 years.
Due to its effect on testosterone, HCG use can also increase estradiol and DHT, although I have not seen data that shows if this increase is proportional to the dose used.
So, the best dose of HCG to sustain normal testicular function while keeping estradiol and DHT conversion to a minimum has not been established.
Some doctors are recommending using 200–500 IUs twice a week for men who are concerned about testicular size or who want to preserve fertility while on testosterone replacement. Higher doses, such as 1,000–5,000 IUs twice a week, have been used but I believe that these higher doses could cause more estrogen and DHT-related side effects, and possibly desensitize the testicles for HCG in the long term. Some doctors check estradiol levels a month after this protocol is started to determine whether the use of the estrogen receptor modulators tamoxifen (brand name: Nolvadex) or anaztrozole (brand name: Arimidex), is needed to counteract any increases in estradiol levels. High estradiol can cause breast enlargement and water retention in men but it is important at the right blood levels to maintain bone and brain health.
******************************************************************************Shippen’s Chorionic Gonadotrophin Stimulation Test (for males under 75 years of age)
Even though there seems not be an accepted and clinically proven protocol to dose HCG, Dr. Eugene Shippen (author of the book “The Testosterone Syndrome”), has developed his own after his own experiences. Most doctors do not follow this protocol but I am showing it here since I get a lot of questions about it.  I have never used this protocol myself since I have been on testosterone replacement for over 15 years.
Dr.  Shippen  has  found  that  a  typical  treatment  course  for  three weeks  is  best  for  determining  those  individuals  who  will  respond well  to  HCG  treatment.  It  is  administered  daily  by  injection  500 units subcutaneously, Monday through Friday for three weeks.   The patient  is  taught  to  self  administer  with  50  Unit  insulin  syringes with  30  gauge  needles  in  anterior  thigh,  seated  with  both  hands free to perform the injection. Testosterone, total and free, plus E2 (estradiol) are measured before starting the protocol and on the third Saturday after 3 weeks of stimulation (he claims that salivary testing may be more accurate for adjusting doses). Studies have shown that subcutaneous injections are equal in efficacy to intramuscular administration.
By measuring the effect on his HCG protocol on total testosterone, he identifies candidates that require testosterone replacement versus those who just require having their testicles “awaken” with HCG to produce normal testosterone. I am yet to see any data that substantiates his approach, however.
Here is how he determines Leydig (testicular) cell function:
1.   If the HCG protocol causes less than a 20% rise in total testosterone he suggests poor testicular reserve of Leydig cell function (primary hypogonadism           or eugonadotrophic    hypogonadism  indicating combined central and peripheral factors).
2.   20-50% increase in total testosterone indicates adequate reserve but slightly depressed response, mostly central inhibition but possibly decreased testicular response as well.
3.  More than 50% increase in total testosterone suggests primarily centrally mediated depression of testicular function.
He then offers these options for treatment for patients depending on the response to HCG and patient determined choices.
1.   If there is an inadequate response ( 20%), then replacement with testosterone will be indicated.
2.   The area in between 20-50% will usually require HCG boosting for a period of time, plus natural boosting or “partial” replacement options.
I   am   yet   to   see   what   he   means   with   natural   boosting!
Dr.  Shippen  believes  that  full  replacement  with  testosterone  is always  the  last  option  in  borderline  cases  since  improvement over time may frequently occur as the testicles’ Leydig cell regeneration may actually happen. He claims that much of this is age dependent. Up to age 60, boosting is almost always successful. In the age range 60-75 is variable, but will usually be clear by the results of the stimulation test. Also, disease related depression of testosterone output might be reversible with adequate treatment of the underlying process  (depression,  obesity,  alcohol,  deficiency, etc.) He claims that this positive effect will not occur if suppressive therapy is instituted in the form of full testosterone replacement.
3.   If there is an adequate response of more than 50% rise in testosterone, there is very good Leydig cell reserve. HCG therapy will probably be successful in restoring full testosterone output without replacement, a better option over the long term and a more natural restoration of biologic fluctuations for optimal response. But I am yet to see any data on long term use of HCG used in this approach! (I invite researchers to do such studies)
4.   Chorionic HCG can be self-administered and adjusted according to response. In younger, high output responders (T > 1100ng/dl), HCG can be given every third or fourth day. This also minimizes estrogen conversion.  In  lower  level  responders  (600-800ng/dl),  or  those with a higher estradiol output associated with full dose HCG, 300- 500 units can be given Mon-Wed-Fri. At times, sluggish responders may  require a  higher dose  to  achieve full  testosterone response.
Dr. Shippen believes in checking salivary levels of free testosterone on the day of the next injection, but before the next injection to determine effecacy  and  to  adjust  the  dose  accordingly.    He claims  that  later  as  Leydig  cell  restoration  occurs,  a  reduction in  dose  or  frequency  of  administration  may  be  later  needed.
5.   He recommends to monitor both testosterone and estradiol levels to assess response to treatment after 2 - 3 weeks after change in dose of HCG as well as periodic intervals during chronic administration. He claims that salivary testing will better reflect the true free levels of  both  estrogens  and  testosterone.  (Pharmasan.com  and  others) Most insurance companies do not pay for salivary testing.  Blood testing is the standard way to test for testosterone and estradiol.
6.   Except for reports of antibodies developing against HCG (he mentions that he has never seen this problem), the claims that there are no adverse effects of chronic HCG administration.
Dr. Shippen’s book was published in the late 90’s.   I know of no physician that uses his protocol.  I have no opinion on its validity.  The idea that testicular function can be improved with cycles of HCG in men with low testosterone caused by sluggish yet functioning Leydig cells is an interesting concept that needs to be studied. I guess that since this protocol requires very close monitoring, many doctors have avoided using it. The off label nature of the protocol’s use of HCG can also make it expensive for patients who will have to pay cash for its use and monitoring.

A very well known doctor in the field of testosterone replacement, Dr. John Crisler (www.allthingsmale.com), recommends 250  IU of HCG twice per week for all TRT patients, taken the day of, along with the day before, the weekly testosterone cypionate injection. After looking at countless lab printouts, listening to subjective reports from patients, and learning more about HCG, he reports to be shifting that regimen forward one day. In other words, his patients who inject testosterone cypionate now take their HCG at 250 IU two days before, as well as the day immediately previous to, their weekly intramuscular shot. All administer their HCG subcutaneously, and dosage may be adjusted as necessary (he reports that rarely more than 350 IU twice weekly dose is required).
For men using testosterone gels, the same dose every third day has anecdotally helps to preserve testicular size (the dose of the gel has to be adjusted after a month of HCG to compensate for the increased testosterone caused by HCG).
Some doctors believe that stopping TRT for a few weeks in which only 1000- 2000 IU HCG weekly is used provides a good way to stimulate testicular function without having to use HCG continuously. I have not seen any data to support this approach. Others believe that cycling HCG on and off while maintaining TRT may prevent any desentization of testicular Leydig cells to HCG.  Again, no data or reports have been published on this approach.
Some men have asked me why we cannot use HCG solely to make our own testicles produce testosterone without the use of TRT along with it. According to Dr. Crisler, using HCG as sole testosterone replacement option does not bring the same subjective benefit on sexual function as pure testosterone delivery systems do—even when similar serum androgen levels are produced from comparable baseline values. However, supplementing the more “traditional” transdermal, or injected options, testosterone with the correct doses of HCG stabilizes blood levels, prevents testicular atrophy, helps rebalance expression of other hormones, and brings reports of greatly increased sense of well-being and libido.  But in excess, HCG can cause acne, water retention, moodiness, and gynecomastia (breast enlargement in men).
Many men have complained that their doctors do not know about HCG and how to use it (I do not blame doctors for being confused!). Some spend a lot of time trying to find doctors to feel comfortable prescribing it. One good way to find out what doctor in your area may be currently prescribing it is to call your local compounding pharmacies to ask them what doctors call them for their patients’ prescriptions.
If you decide (with the agreement of your doctor) that you want to use HCG with your TRT regimen at 500 IU per week, then you will need 2000 IU per month. I personally do not like to have diluted HCG sitting in my fridge for over six weeks (HCG may degrade with time after mixed in with bacteriostatic water even when refrigerated). So, a 3000 or 35000 IU vial should suffice for 6 weeks.
Your doctor can call in the following prescription to a compounding pharmacy (shop around for best prices. I use APSmeds.com):
Human Chorionic Gonadotropin, 3500 IU (or any other IU amount) vial, #1, 3 refills, as directed
Every 5 weeks, remember to call the compounding pharmacy to get the next shipment of HCG so that you do not run out.
After reading this section, you probably agree with me that using HCG requires a lot of discipline since you have to remember to inject it weekly in addition to your weekly or bi-weekly testosterone injection. But I know of many men who have that type of commitment since they do not want testicular size reduction. And many of us may just be fine with our reduced testicular size as long as testosterone is actually doing its job in improving our sex drive. And some lucky men do not get testicular atrophy at all on testosterone (those with large testicles to start with usually do not seem to complain about shrinkage as much as men starting with smaller testicular size before TRT). So it is a personal decision at the end!
As you will read in the section “HPGA dysfunction” HCG is also used in a protocol in combination with clomiphene and tamoxifen to attempt to bring the body’s own testosterone production back to normal when someone needs to stop testosterone or anabolic steroids after long-term use. This protocol only works for those who started testosterone or anabolic steroids at normal baseline testosterone levels (bodybuilders and athletes) and it is not intended to work in those of us who had testosterone deficiency (hypogonadism) to start with.
As you can tell, there is no agreement on the correct dose and frequency of HCG.   I really hope that researchers in the endocrine field compare different protocols in a controlled manner so that we can settle this issue once and for all. I encourage pharmaceutical companies to seek approval for using HCG for prevention of testicular atrophy in men using TRT. This new indication can prove to be lucrative as the TRT market grows over 2 billion dollars a year in the United States as more men become aware of hypogonadism treatment options.
PERSONAL COMMENT: I have used HCG to reverse testicular shrinkage and it works extremely well not only for that purpose but also for boosting sexy drive. I do have to remind myself that as soon as I stop using it, testicular atrophy will recur.  I have recently started using it in small doses (250 IU twice a week subcutaneously) which seems to be a good maintenance regimen for me.  I get my HCG from compounding pharmacies at $70 per 10,000 IUs since the pharmaceutical commercial products are too expensive and rarely paid by insurance for testicular atrophy. I remind men that HCG can increase your estradiol and DHT blood levels, so it is important to have your doctor retest you for both of these values after you start. Lowering testosterone dosage may be required when using HCG along side with TRT since HCG can have an additive effect on testosterone blood levels. But we need so much more data on HCG to stop making assumptions and using protocols that are endorsed by anecdotal information.
For more Information, please fill this form and someone will get back with you:http://www.apsmeds.com/nv.html

New Video by Nelson Vergel: Practical Tips for Optimum Testosterone Replacement Therapy

I am glad to announce that my short video has been posted on youtube.  I summarize in it all I know about testosterone replacement therapy including how to maximize benefits and minimize side effects.

Popular Diabetes Drug Decreases Testosterone in Men with Diabetes

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2012.04510.x/abstract




Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: A randomized double blind placebo-controlled study








Abstract


Objectives


Pioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied.




Research design and methods


A randomized, double blind, placebo-controlled trial with six months follow-up. Fifty (25 in each group) eugonadal men (well virilized and total testosterone ≥ 12 nmol/L) with T2DM, aged 30-55 yr, and HbA1c of ≤ 7.5%, were randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy.




Results


As compared to placebo, six months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16.1 to 14.9 vs 17.1 to 17.0 nmol/L; p = 0.031), calculated free testosterone (p = 0.001) and bioavailable testosterone (p = 0.000) despite significant increase in sex hormone binding globulin (p = 0.000). Plasma androstenedione (∆4) level increased (1.5 to 1.9 ng/ml; p = 0.051) following pioglitazone therapy. The decrease in testosterone was independent of change in body weight, body fat, and HbA1c.




Conclusion


Pioglitazone therapy significantly decreases total, free and bioavailable testosterone in eugonadal men with T2DM. The effects of these alterations need to be determined by further long term studies.

Popular Diabetes Drug Decreases Testosterone in Men with Diabetes

http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2265.2012.04510.x/abstract

Effect of pioglitazone on testosterone in eugonadal men with type 2 diabetes mellitus: A randomized double blind placebo-controlled study


AbstractObjectivesPioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied.Research design and methodsA randomized, double blind, placebo-controlled trial with six months follow-up. Fifty (25 in each group) eugonadal men (well virilized and total testosterone ≥ 12 nmol/L) with T2DM, aged 30-55 yr, and HbA1c of ≤ 7.5%, were randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy.ResultsAs compared to placebo, six months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16.1 to 14.9 vs 17.1 to 17.0 nmol/L; p = 0.031), calculated free testosterone (p = 0.001) and bioavailable testosterone (p = 0.000) despite significant increase in sex hormone binding globulin (p = 0.000). Plasma androstenedione (∆4) level increased (1.5 to 1.9 ng/ml; p = 0.051) following pioglitazone therapy. The decrease in testosterone was independent of change in body weight, body fat, and HbA1c.ConclusionPioglitazone therapy significantly decreases total, free and bioavailable testosterone in eugonadal men with T2DM. The effects of these alterations need to be determined by further long term studies.

Testosterone Blood Tests Should Be Done in a Fasted State

Thanks to Dr Scally for this reference (http://michaelscally.blogspot.com )







Serum Testosterone Decrease After A Mixed Meal Independent Of SHBG And Gonadotrophins








The secretion and concentration of plasma sex steroids can be affected by both genetic and environmental factors. Testosterone levels have a circadian rhythm with the highest circulating levels during the morning. Sampling for S-T determination is recommended to take place in morning hours between 07 and 11.00 h after a normal night’s sleep to have a truly representative assessment and avoid false low concentrations.




Most clinical protocols have no food intake restrictions prior to blood sampling for S-T assessment. However, earlier reported human studies have indicated an effect of food intake on serum testosterone levels, suggesting that food intake may influence the diurnal rhythm. On the other hand, previous studies have also shown that mixed carbohydrate and protein meal has no effect on total or free testosterone concentrations while acute fat intake decreases S-testosterone level and chronic high fat intake increases S-testosterone level. It has been hypothesized that acute fat intake increases the level of chylomicrons, which can reduce LH-stimulated testosterone production in vitro. However, these findings were not confirmed in vivo in a study that changed dietary fat intake from 37% to 64%.




Hence, several factors may be expected to affect the circadian rhythm of testosterone level and the impact of diet on serum testosterone level needs further investigation. Clinical evaluation of male gonadal activity often requires investigation of the hypothalamus-pituitary-testis axis. Accurate biochemical determinations are crucial to identify and exclude confounding factors that influence testosterone level. Therefore, researchers undertook a strictly controlled crossover study to investigate the effect of fed state compared to fasting state on S-T, S-LH and S-SHBG serum levels during the morning in healthy men.




In summary, their study verifies that food intake decreases testosterone level in serum in healthy men, with a 30% reduction in testosterone compared to the fasting condition. They recommend that the serum testosterone should be measured in starving condition in the morning to reduce the risk of inaccurate low testosterone levels in the investigation of men where there is clinical suspicion of hypogonadism.







Lehtihet M, Arver S, Bartuseviciene I, Pousette Å. S-testosterone decrease after a mixed meal in healthy men independent of SHBG and gonadotrophin levels. Andrologia. http://onlinelibrary.wiley.com/doi/10.1111/j.1439-0272.2012.01296.x/abstract

Testosterone Blood Tests Should Be Done in a Fasted State

Thanks to Dr Scally for this reference (http://michaelscally.blogspot.com )


Serum Testosterone Decrease After A Mixed Meal Independent Of SHBG And Gonadotrophins
The secretion and concentration of plasma sex steroids can be affected by both genetic and environmental factors. Testosterone levels have a circadian rhythm with the highest circulating levels during the morning. Sampling for S-T determination is recommended to take place in morning hours between 07 and 11.00 h after a normal night’s sleep to have a truly representative assessment and avoid false low concentrations.
Most clinical protocols have no food intake restrictions prior to blood sampling for S-T assessment. However, earlier reported human studies have indicated an effect of food intake on serum testosterone levels, suggesting that food intake may influence the diurnal rhythm. On the other hand, previous studies have also shown that mixed carbohydrate and protein meal has no effect on total or free testosterone concentrations while acute fat intake decreases S-testosterone level and chronic high fat intake increases S-testosterone level. It has been hypothesized that acute fat intake increases the level of chylomicrons, which can reduce LH-stimulated testosterone production in vitro. However, these findings were not confirmed in vivo in a study that changed dietary fat intake from 37% to 64%.
Hence, several factors may be expected to affect the circadian rhythm of testosterone level and the impact of diet on serum testosterone level needs further investigation. Clinical evaluation of male gonadal activity often requires investigation of the hypothalamus-pituitary-testis axis. Accurate biochemical determinations are crucial to identify and exclude confounding factors that influence testosterone level. Therefore, researchers undertook a strictly controlled crossover study to investigate the effect of fed state compared to fasting state on S-T, S-LH and S-SHBG serum levels during the morning in healthy men.
In summary, their study verifies that food intake decreases testosterone level in serum in healthy men, with a 30% reduction in testosterone compared to the fasting condition. They recommend that the serum testosterone should be measured in starving condition in the morning to reduce the risk of inaccurate low testosterone levels in the investigation of men where there is clinical suspicion of hypogonadism.

Lehtihet M, Arver S, Bartuseviciene I, Pousette Å. S-testosterone decrease after a mixed meal in healthy men independent of SHBG and gonadotrophin levels. Andrologia. http://onlinelibrary.wiley.com/doi/10.1111/j.1439-0272.2012.01296.x/abstract

SEASONAL FLUCTIONATIONS IN TESTOSTERONE:ESTROGEN RATIO IN MEN FROM THE SOUTHWEST UNITED STATES.

http://www.ncbi.nlm.nih.gov/pubmed/22790643AbstractINTRODUCTION:Though controversial, seasonal variations in testosterone (T) have been observed in several populations of men throughout the world. This finding might impact screening and treatment of hypogonadism.AIM:We examined the circannual patterns of sex hormones in the southwest United States.METHODS:A prospectively assembled database of almost 11,000 patients in a men's health practice was used to collect data on T, estradiol (E), sex hormone binding globulin (SHBG), follicle stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone (DHEA). Patient age, address, and date of visit were recorded. Of note, T:E ratio and free T were calculated values.MAIN OUTCOME MEASURES:The data were grouped by month and by season (3 month intervals beginning with June, July, and August as summer). ANOVA was used to compare hormone levels between seasonal and monthly data sets with P < 0.05 regarded as statistical significance.RESULTS:Statistically significant differences in E (P = 0.02), T:E ratio (P < 0.01), FSH (P = 0.02), and SHBG (P < 0.01) were observed between seasons. Peak-to-trough variations were as follows: 6% for E, 16.5% for T:E ratio, 11.0% for FSH, and 11.6% for SHBG. The T:E ratio peaked in the spring and was at its nadir in the fall. No differences in T (P = 0.21), LH (P = 0.25), free T (P = 0.08), and DHEA (P = 0.11) were observed.CONCLUSION:Statistically significant evidence of variation in estradiol and T:E ratio were identified in the men included in this study. While this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings.

Pain Killers Lower Testosterone: Opioid-Induced Androgen Deficiency (OPIAD)

Accompanying the upsurge in the use of long-term opioid therapy has been an increase in the occurrence of opioid associated endocrinopathy, most commonly manifested as an androgen deficiency and therefore referred to as opioid associated androgen deficiency (OPIAD).

Smith HS, Elliott JA. Opioid-Induced Androgen Deficiency (OPIAD). Pain Physician 2012;15(3 Suppl):ES145-56. http://www.painphysicianjournal.com/2012/july/2012;15;ES145-ES156.pdf
Opioid therapy is one of the most effective forms of analgesia currently in use. In the past few decades, the use of opioids as a long-term treatment for chronic pain has increased dramatically. Accompanying this upsurge in the use of long-term opioid therapy has been an increase in the occurrence of opioid associated endocrinopathy, most commonly manifested as an androgen deficiency and therefore referred to as opioid associated androgen deficiency (OPIAD). This syndrome is characterized by the presence of inappropriately low levels of gonadotropins (follicle stimulating hormone and luteinizing hormone) leading to inadequate production of sex hormones, particularly testosterone. Symptoms that may manifest in patients with OPIAD include reduced libido, erectile dysfunction, fatigue, hot flashes, and depression. Physical findings may include reduced facial and body hair, anemia, decreased muscle mass, weight gain, and osteopenia or osteoporosis. Additionally, both men and women with OPIAD may suffer from infertility. While the literature regarding OPIAD remains limited, it is apparent that OPIAD is becoming increasingly prevalent among chronic opioid consumers but often goes unrecognized. OPIAD can have a significant negative impact on the the quality of life of opioid users, and clinicians should anticipate the potential for its occurrence whenever long-term opioid prescribing is undertaken. Once diagnosed, treatment for OPIAD may be offered utilizing a number of androgen replacement therapy options including a variety of testosterone preparations and, for female patients with OPIAD, dehydroepiandrosterone (DHEA) supplementation. Follow-up evaluation of patients receiving androgen replacement therapy should include a review of any unresolved symptoms of hypogonadism, laboratory evaluation, and surveillance for potential adverse effects of androgen replacement therapy including prostate disease in males.