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Sunday, March 31, 2013

Effective Hair Loss Treatment with Eyelash Growth Drug

Bimatoprost is known as the brand name Latisse.  It was used for glaucoma for years and it was found that one of its side effects was eyelash growth.  So it was approved for that purpose with the name Latisse.  Emerging data show that this drug may also work to reverse hair loss in men and women.
Posted: 30 Mar 2013 07:24 AM PDT


Khidhir KG, Woodward DF, Farjo NP, et al. The prostamide-related glaucoma therapy, bimatoprost, offers a novel approach for treating scalp alopecias. Faseb J 2013;27(2):557-67.  http://www.fasebj.org/content/27/2/557.long 

Balding causes widespread psychological distress but is poorly controlled. The commonest treatment, minoxidil, was originally an antihypertensive drug that promoted unwanted hair. We hypothesized that another serendipitous discovery, increased eyelash growth side-effects of prostamide F(2alpha)-related eyedrops for glaucoma, may be relevant for scalp alopecias. Eyelash hairs and follicles are highly specialized and remain unaffected by androgens that inhibit scalp follicles and stimulate many others. Therefore, we investigated whether non-eyelash follicles could respond to bimatoprost, a prostamide F(2alpha) analog recently licensed for eyelash hypotrichosis. Bimatoprost, at pharmacologically selective concentrations, increased hair synthesis in scalp follicle organ culture and advanced mouse pelage hair regrowth in vivo compared to vehicle alone. A prostamide receptor antagonist blocked isolated follicle growth, confirming a direct, receptor-mediated mechanism within follicles; RT-PCR analysis identified 3 relevant receptor genes in scalp follicles in vivo. Receptors were located in the key follicle regulator, the dermal papilla, by analyzing individual follicular structures and immunohistochemistry. Thus, bimatoprost stimulates human scalp follicles in culture and rodent pelage follicles in vivo, mirroring eyelash behavior, and scalp follicles contain bimatoprost-sensitive prostamide receptors in vivo. This highlights a new follicular signaling system and confirms that bimatoprost offers a novel, low-risk therapeutic approach for scalp alopecias.


Possible Mechanism For The Stimulation Of Hair Growth By Bimatoprost

Bimatoprost stimulates eyelash growth in vivo, human scalp hair growth in organ culture, and mouse pelage hair growth in vivo. In our hypothesis, these effects are due to bimatoprost binding to appropriate receptors on the plasma membrane of cells in the regulatory dermal papilla in the hair bulb (middle panel). This probably stimulates intracellular signaling pathways, which trigger alterations in the gene expression of paracrine signals and their extracellular release. Some of these factors would leave the dermal papilla, crossing the basement membrane, isolating it from the rest of the follicle, to stimulate the coordinated activity of the keratinocytes and melanocytes to produce increased hair growth and pigmentation. Red dots indicate FP and/or prostamide F2α receptors, blue arrows indicate direction of movement of paracrine factors.

For more information on a compounded version of the drug: Click Here





Monday, March 18, 2013

Testosterone+ HCG Preserves Healthy Sperm in Men on Testosterone Replacement Therapy (Injections and gels)





Tung-Chin  Hsieh, Alexander  W. Pastuszak, Kathleen Hwang and Larry I. Lipshultz*,†



From the Division of Urology, University of California-San Diego (TCH), San Diego, California, Scott Department of Urology, Baylor College of
Medicine (AWP, LIL), Houston, Texas, and Department of Urology (KH), Brown University School of Medicine, Providence, Rhode Island






Purpose: Testosterone replacement therapy results in decreased serum gonadotropins (hormones produced by the pituitary gland- LH and FSH- that jump start testicular function) and  intratesticular testosterone (inside the testicles), and  impairs spermatogenesis (sperm production), leading to azoospermia (no viable sperm) in  40%  of patients. However, intratesticular  testosterone can  be maintained during testosterone replacement therapy with co-administration of low dose human chorionic gonadotropin, which  may  support continued spermatogenesis in patients on testosterone replacement therapy.

Materials and Methods: We retrospectively reviewed the  records of hypogonadal men  treated with testosterone replacement therapy and  concomitant low dose  human chorionic gonadotropin (HCG). Testosterone replacement consisted of daily  topical gel or weekly intramuscular injection with intramuscular human chorionic gonadotropin (500 IU) every  other daySerum and  free testosterone, estradiol, semen parameters and  pregnancy rates were  evaluated before  and  during therapy.

Results: A total of 26 men  with a mean age  of 35.9  years were  included in  the study. Mean followup  was 6.2 months. Of the men  19 were  treated with injectable testosterone and   7  were  treated with transdermal gel.  Mean serum hormone levels   before   vs  during treatment  were   testosterone  207.2   vs  1,055.5  ng/dl (p<0.0001), free testosterone 8.1 vs 20.4 pg/ml  (p = 0.02) and  estradiol 2.2 vs 3.7 pg/ml  (p = 0.11).  Pretreatment semen parameters were  volume 2.9 ml,  density 35.2 million per ml, motility 49.0% and  forward progression 2.3. No differences in semen parameters  were  observed during greater than 1  year of followup. No impact on semen parameters was  observed as  a function of testosterone formulation. No patient became azoospermic during concomitant testosterone replacement and  human chorionic gonadotropin therapy. Nine  of 26 men  contributed to pregnancy with the  partner during followup.

Conclusions: Low dose  human chorionic gonadotropin appears to maintain semen  parameters in hypogonadal men  on testosterone replacement therapy. Concurrent testosterone replacement and  human  chorionic gonadotropin use  may preserve fertility in hypogonadal males who desire fertility preservation while  on testosterone replacement therapy.


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 Low-Dose Human Chorionic Gonadotropin Maintains Intratesticular Testosterone in Normal Men with Testosterone-Induced Gonadotropin Suppression


This study shows that HCG can keep intratesticular (inside the testes) testosterone - ITT normal even when they are exposed to testosterone injections. An HCG dose of 500 IU every other day increased ITT to levels higher than baseline. All other doses failed to achieve normalization of baseline ITT. ITT is crucial for Leydig cells to work properly so that they do not atrophy (lose volume due to inactivity)

http://www.ncbi.nlm.nih.gov/m/pubmed/15713727/


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More information on HCG+TRT

Saturday, March 16, 2013

Most Men on Androgel and Testim Stop Using Them





Medication Adherence and Treatment Patterns for Hypogonadal
Patients Treated with Topical Testosterone Therapy: A Retrospective Medical Claims Analysis


Michael Jay Schoenfeld, MA, Emily Shortridge, PhD, Zhanglin Cui, PhD, and David Muram, MD

Eli Lilly and Company, Indianapolis, IN, USA DOI: 10.1111/jsm.12114

A B S T R A C T

Introduction.  There is limited information  on adherence to topical testosterone replacement  therapy (TRT) among hypogonadal  men.
Aim.  To determine  adherence  rates among men treated  with topical testosterone gels and to examine factors that may influence adherence,  including age, presence of a specific diagnosis, and index dose.

Methods.  Included were 15,435 hypogonadal men, from the Thomson Reuters MarketScan® Database, who had an initial topical testosterone prescription  in 2009 and who were followed for 12 months.

Main Outcome Measures.  Adherence to testosterone was measured by medication possession ratio (MPR), with high adherence  defined as >0.8. Persistence  was defined as the duration  of therapy from the index date to the earliest of the following events: end date of the last prescription, date of the first gap of >30 days between prescriptions,  or end of the study period (12 months).

Results.  Adherence to topical TRT was low. By 6 months,  only 34.7% of patients had continued  on medication; at 12 months, only 15.4%. Adherence rates were numerically similar among men who received AndroGel® or Testim® topical gels and did not differ among men of different age groups. Approximately 80% of patients  initiated  at the recommended dose of 50 mg/day. Over time, an increased proportion of men used a higher dose. This change was the result of dose escalation, rather  than of greater  adherence  among men initiating  therapy  at a high dose. Dose escalation  was seen as early as 1 month  into  therapy.  Approximately  50%  of men  who  discontinued  treatment resumed therapy; most men used the same medication  and dose.

Conclusions. Discontinuation rates are high among hypogonadal men treated with testosterone gels, irrespective of their age, diagnosis, and index dose. Further study, evaluating other  measurable factors associated with low adherence among patients receiving topical TRT, may lead to interventions designed to improve adherence with therapy

COMMENTS:

About 50% of patients who were followed over time resumed TRT. It is possible that some patients  experienced  alleviation of symptoms and were not sure they needed to remain on therapy. Once therapy was discontinued and symptoms recurred  in some patients, the benefits of replacement  therapy may have become clearer;   thus,   prompting  these   men   to  restart therapy  at the same effective dose. 

An important limitation  of the study is that  claims data do not  include important patient level data, such as symptoms, reasons for discontinuation (e.g., application method), side effects (e.g., skin reaction), testosterone  levels,  responses  to  therapy,  and  so  forth. While  perception  of efficacy has significant effect on  patient  adherence,   this  study  was unable  to assess severity of symptoms or of symptomatic relief, once patients initiated  therapy.

The study was unable to identify characteristics that were associated with the time patients would be on therapy  before treatment was interrupted or who would resume therapy after a brief interruption. Most  patients  who  resumed  therapy  did  so  by using the  same topical TRT agent  and the  same dose they used prior to the interruption. It is possible that these patients perceived efficacy, were proficient  in the application method,  and possibly had a prescription  that  they  were able to use or refill without  the  need for an office visit. Only  a small percentage  of patients  using topical therapy resumed therapy by using a different method  or a change in the dosing regimen.


Lesson:

Patients on testosterone should have their blood levels and symptoms evaluated after a few weeks on therapy.  Depending on these follow up results, dose adjustment or change of delivery method should be explored as well as other issues that may potentially affect efficacy and adherence (life style, other medications, body mass index, etc).  Expectations should also be clearly described at the start of therapy (for more on what to expect, read this ) so that patients have realistic views.  Stamina and sexual function are multifactorial and testosterone blood levels are only part of the puzzle.

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