Archive for 'pituitary'

Testosterone Restart Failure

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I just wanted to get everyone up to date on a relatively new way to boost testosterone for hypogonadal males whose cause of low testosterone is not a diagnosed primary (testicular failure) or secondary (issue with hypothalamus or pituitary gland).  In short, medical professionals call such states idiopathic, meaning cause unknown.  For example, some men with low testosterone suffer from insulin resistance, which can lower SHBG to levels low enough that free testosterone increases above the normal range, causing the homeostatic state to finally settle into a low total testosterone state as the body dumps the excess free T.  However, I am not aware of any study which conclusively proves this point.  Therefore, as in my case, decreasing insulin resistance by diet, exercise, and in my case the use of the over-the-counter product Ortho Molecular CM Core.  The later supplement decreased my A1C from 6.8 to 5.1 in about 4 months – an amazing result.

I recently attempted this approach, a therapy which consists of low dose Clomid at 25mg/day for 6 weeks.  In the past, many attempted high dose Clomid of 100mg-150mg/day for a few weeks to a month.  Side effects with dosages this high rarely are well tolerated and include seeing “tracers”, loss of libido, and mood swings.

Clomid is actually a selective estrogen receptor modulator, or SERM.  The drug, available by prescription only, acts on some tissues as an estrogen and in others this SERM will block estrogen. In males estrogen is blocked or inhibited in the hypothalamus resulting in an interesting effect:  the stimulation of Gonadatropin Releasing Hormone (GnRH) which then stimulates the pituitary gland to kick up its production of LH (leutinizing hormone) in the pituitary.  LH then stimulates the Leydig cells in the testicles to pump out testosterone.

One other side effect of Clomid to keep in mind is that over the long term, and especially at higher dosages, the pituitary gland is desensitized to GnRH.  Therefore, a short run of low dose Clomid,if successful in increasing testosterone production, is best looked at as a way to kick start the hypothalamus and pituitary gland into successfully working at full potential.  Upon cessation however, if the cause of low testosterone is still unknown or unaddressed, testosterone levels often drop to pretreatment levels.

One study of 36 men with average total testosterone of 248 ng/dl, placed the subjects on 25 mg/day of Clomid.  After 4-6 weeks the men’s average testosterone was a hefty 610 ng/dl.  This is a nice boost indeed, especially for what is considered a relatively low dose of Clomid.

My recent foray into this treatment ended unsuccessfully.  Prior to treatment, I ceased all TRT for two weeks.  Total T plummeted to 70ng/dL.  After six weeks my levels stood at a paltry 195ng/dL.  However, in my particular case, due in part to the length of time on TRT – over 15 years – the testicular atrophy due to such long use may have been addressed – and in my particular case has successfully been addressed in the past – with high dosages of Human Chorionic Gonadatropin (HCG) injected subcutaneously into the stomach fat using insulin needles.  Doses of 1000-1500IU every other day for 20 days are usually enough to really kick in Leydig cell production of testosterone assuming no issue exists with the function of these cells. At these dosages the need to control the conversion of testosterone to Estradiol or E2 (a potent estrogen) is sometimes necessary.  This conversion process, known as aromatization, typically occurs in the liver and body fat surrounding internal organs – also known as adipose fat.  Small dosages of the aromatase inhibitor Arimidex at .05mg/day usually keeps this process under control, and such dosages can be provided in capsule form by a good compounding pharmacy.  The amount needed varies from person to person, with some requiring more, and many hyper-responders requiring less.

The six week program of Clomid did increase my LH and follicle stimulating hormone to the high end of normal and quite possibly I could have seen an increase in testosterone given more time.  However the concern of desensitizing my pituitary to GnRH lead to the cessation of the Clomid and restarting the Testim for TRT.

Other protocols exist and mileage will vary.  Some add in Tamoxifen, another SERM, to work with the Clomid and also help combat the desensitization of the pituitary gland to GnRH.  I have seen so many protocols out there I can only conclude that the best protocol likely varies depending on the person and the underlying cause of idiopathic hypogonadism.

Testosterone Facts and Education

So just how does the male body produce testosterone? While the number of systems that can impact testosterone production is large in number, the basics are rather simple. Let’s start at the hypothalamus and work our way down.

  • The hypothalamus produces gonadotropin-releasing hormone (GnRH)
  • This hormone triggers the anterior pituitary gland to produce two other hormones
  • These two hormones are luteinizing hormone (LH) and follicle-stimulating hormone (FSH)
  • LH stimulates the Leydig cells in the testicles to produce testosterone while FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body and acts synergistically with LH in male reproductive health.

Simple enough, but what happens is one or more of these systems is compromised in some manner? Defects in the hypothalamus or pituitary gland that compromise the release of GnRH (and subsequently FSH and LH) or adversely affect the release of FSH or LH from the anterior pituitary lead to what is known as secondary hypogonadism. A defect in the testicles that causes a reduction or cessation of gonadal response to LH is characterized as primary hypogonadism. There are many causes of both primary and secondary hypogonadism. The link lists only some of the causes. Also check out this link. Hypogonadism that is present absent any of these conditions or any other known conditions that affect male testosterone production comes under the heading idiopathic hypogonadism. This later label correctly describes my own condition.

Typically a doctor will order a test that measures the total serum testosterone. This is a simple blood test that provides a number, usually in the units of nanograms per deciliter (ng/dl). Normal values vary by the lab performing the test on the blood sample, but typically values are from around 300ng/dL to 1000ng/dl. However, caution should be used in using this raw value as an stark indicator of hypogonadism. For some men presenting with low normal values or even normal values symptoms of low testosterone are often seen. Therefore the entire clinical picture is needed to ensure treatment is provided even in the face of so-called normal results. Also, an entire workup of the thyroid function as well as adrenal function is necessary. Any issue with either of these glands can often lead to hypogonadism or mimic they symptoms of hypogonadism. Also, an understanding of any issues with these glands will guide the treating physician in the selected treatment. As an example, long-standing hypothyroidism will impair the absorption of transdermal testosterone due to build-up of mucin in the skin of people. Mucin causes the skin to thicken impairing absorption of transdermal testosterone.

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