Some of us have been there. Look up & research Klinefelters Mosaic Syndrome
1st - change your name from loser to winner. Attitude is what counts.
2nd - Get your male & female blood tests
3rd - Find a good endo that does hormone as his/her main speciality. Most are diabeties docs.
Tests for Males
• Total Testosterone
• Bioavailable Testosterone (AKA "Free and Loosely Bound")
• Free Testosterone (if Bioavailable T is unavailable)
• DHT
• Estradiol (specify the "sensitive" assay for males)
• LH
• FSH
• Prolactin
• Cortisol
• Thyroid Panel
• CBC
• Comprehensive Metabolic Panel
• Lipid Profile
• PSA (if over 40)
• IGF-1 (if HGH therapy is being considered)
FOLLOW-UP LABS
Two weeks after initiating a transdermal, or five weeks after the
first injection start of gel:
• Total Testosterone
• Bioavailable Testosterone
• Free Testosterone (if Bioavailable T is still unavailable)
• Estradiol (specify the Extraction Method, or "sensitive" assay for males)
• DHT (especially if patient is using a transdermal delivery system)
• FSH (3rd Generation—ultrasensitive assay this time)
• CBC
• Comprehensive Metabolic Panel
• Lipid Profile
• PSA (for more senior patients)
• IGF-1 (if GH Therapy has been initiated already)
INDIVIDUAL ASSAYS EXPLAINED
TOTAL TESTOSTERONE
This is the assay your patients will most focus on. It's also the
one physicians who do not understand TRT will use to deny patients
the testosterone supplementation they want, and need, when Total T
is at low-normal levels. Total T is important for titration of
dosing, but its relevance is reduced in older men (by virtue of
their increased serum concentrations of SHBG), in favor of:
BIOAVAILABLE TESTOSTERONE
Where we actually get the "bang" for the hormonal buck, so to speak.
This is the actual amount the body has available for use, as the
concentration of hormone available within the capillary beds
approximates the sum of the Free Testosterone plus that which is
loosely bound to carrier proteins, primarily albumin. If Bio T is
not readily available, Free T may be a second choice substitute, as
Bio T and Free T serum concentrations are well correlated.
DHT
This assay is especially important to draw, up-front and at follow-
up, if a transdermal testosterone delivery system is preferred by
the patient. I'll explain why later. DHT level may also help
indicate cause for ED symptoms.
ESTRADIOL
There are several reasons why this assay is VERY important, and
should not be ignored in ANY hypogonadism work-up (or subsequent
regimen). First, you definitely need to draw a baseline. Next,
elevated estrogen can, in and of itself, explain hypogonadal
symptoms. If E is elevated, controlling serum concentrations
(usually with an aromatase inhibitor, which prevents conversion of T
into E) may suffice in clearing the symptoms of hypogonadism. And
finally, rechecking it after beginning the initial dose of
testosterone will give the astute physician valuable information as
to how the patient's individual hormonal system functions, as well
as making sure estrogen does not elevate inappropriately secondary
to the testosterone supplementation.
I don't waste time and money drawing estrone and estriol. E2 is the
player of interest here. Unless you specify a `sensitive' assay for
male patients, the lab will run the Rapid Estradiol for fertility
studies in females, which is useless for our purpose here. Quest
Diagnostics calls this their Estradiol by Extraction Method.
Some practitioners believe that it is only the T/E ratio which is
significant, and therefore, as long as E "appropriately" rises with
elevations in T, all is well. However, the absolute concentration of
E is of concern, too, especially in light of new information
pointing to elevated estrogen as cause, or adjunctively encouraging,
several serious disease processes, including prostate and colon
cancer.
LH
As everyone knows, it is LH which stimulates the Leydig cells of the
testes to produce testosterone. A caveat, however: LH has a half-
life of only about 30 minutes. When you combine this fact with the
absolute pulsatile nature of its pituitary release, care must be
taken to not place too much weight upon a single draw. A luxury
would be to acquire serial draws, say, twenty minutes apart.
However, such would be both inconvenient and probably prohibitively
expensive for the patient. The most important reason to assay the
gonadotrophins is to differentiate between primary and secondary
(hypogonadotrophic) hypogonadism.
FSH
The eight hour half-life of this hormone makes it a better marker
for gonadotrophin production. It is also less an acute phase
reactant to varying serum androgen and estrogen levels than LH.
Greatly elevated FSH levels could signal a gonadotrophin-secreting
pituitary tumor.
Of note, I run FSH (but not LH) on the follow-up labs, the new third
generation ("sensitive") assay, to determine the magnitude of HPTA
suppression secondary to androgen therapy. It also provides valuable
information for those patients undergoing TRT who are interested in
the state of their fertility.
PROLACTIN
A very important hormone, and must not be overlooked on initial work-
up. Approaching five percent of hypogonadotrophic hypogonadism is
associated with hyperprolactinemia, due to inhibition of
hypothalamic release of LHRH. Its serum concentration must be
maintained within physiological range (meaning neither too high nor
too low). Greatly elevated hyperprolactinemia, or hyperprolactinemia
plus a Total Testosterone less than 150ng/dL, equals a trip to an
Endocrinologist for an MRI of the sella turcica.
CORTISOL
True Anti-Aging medicine must be well-familiarized with the ins and
outs of this hormone, the only one our bodies cannot live without.
Elevated levels can cause secondary (hypogonadotrophic)
hypogonadism. I try controlling elevated cortisol with
Phosphatidylserine, 300mg QD, with good results. It is just as
important to watch for depressed cortisol levels, as well. The assay
of choice for that condition is a 24-hour urine.
THYROID PANEL
I have, for my own convenience, omitted the specifics of the
obligatory thyroid function panel you certainly will want to run.
Hypothyroidism mimics hypogonadism in several of its effects.
CBC
This is just good medicine. Ruling out anemia is important, of
course, as it may be a cause for the fatigue which brought the
patient into your office. You also want to establish baseline H&H,
for those rare cases where polycythemia becomes a problem (and we
are reminded smokers are at increased risk for polycythemia). Above
18.0/55.0 TRT is withheld, and therapeutic phlebotomy recommended.
CMP
Again, just good medicine. Baseline for sodium (which may elevate
initially secondary to androgen supplementation) is important. We
also want to see LFT's, as elevations in same secondary to androgen
supplementation are listed as a possible side effect in the product
literature (although I have yet to see this actually happen). I like
the BUN/creatinine ratio as a marker for hormonal hemo-
concentration, and also it gives me a hint of how compliant the
patient will be (because I always tell them to make sure to drink
plenty of water while fasting for the test).
Lipid Panel
This is drawn to provide your bragging rights when you drop the CHOL
30 points, thanks to your own good administration of TRT. You should
expect to see lowered TRIG and LDL's, too. Be advised, this will not
happen if you choose to elevate their androgens above the top
of "normal" range, i.e. providing what amounts to an anabolic
steroid cycle. Of course, this would no longer constitute TRT, as
the practitioner would then be choosing to damage the health and
well-being of the patient.
HDL does frequently drop a bit, but that is believed to be due to
increased REVERSE cholesterol transport; so much of the plaque is,
after being scavenged from the lining of the CV system by HDL, now
being chewed up by the liver. Androgens also elevate hepatic lipase,
and this may have an effect. The important thing to keep in mind is
that TRT inhibits foam cell formation.
PSA
For all patients over 40. Even though prostate CA is rare in men
under the age of fifty, we don't want it happening on our watch, do
we? At this time, rises in PSA above 0.75 are a contraindication to
TRT (until follow-up by a Urologist). You may find that, at the
initiation of TRT in older men, when serum androgen levels are
accelerating, PSA may, too. This is especially true when transdermal
delivery systems are employed, because they more greatly elevate
DHT. Once T levels have stabilized, PSA drops back down to roughly
baseline. You won't really see gross elevations in PSA secondary to
TRT administration in younger patients. New TRT patients need to be
cautioned, and reminded, to abstain from sexual relations prior to
the draw, as they may now be enjoying greatly elevated amounts of same.
I get a PSA up front on my over 40 patients, at the one month follow-
up in my more senior patients, and every six months after that. DRE
(Digital Rectal Exam) is recommended twice per year as well,
although the American Academy of Clinical Endocrinologists
backs "every six to twelve months" in their 2002 Guidelines for
treating hypogonadotrophic patients with TRT.
IGF-1
For those who are considering the addition of GH to their Anti-Aging
regimen. IGF-1 will rise from testosterone supplementation, and vice
versa. Let's grab a baseline now, before that happens.
THINGS TO LOOK OUT FOR:
CO-MORBIDITIES. Currently, only breast and active prostate cancer
are absolute contraindications for TRT. Patients with serious
cardiac, hepatic or renal disease must be monitored carefully due to
possible edema secondary to sodium retention. Also, TRT may
potentiate sleep apnea in some chronic pulmonary disease patients,
although studies have also shown it can actually ameliorate the
symptoms of sleep apnea.
DRUG INTERACTIONS. TRT decreases insulin or oral diabetic medication
requirements in diabetic patients. It also increases clearance of
propranolol, and decreases clearance of oxyphenbutazone in those
receiving such medications. TRT may increase coagulation times as
well.
TESTOSTERONE DELIVERY SYSTEMS
Now we have to decide, TOGETHER with our patient, what form of
testosterone delivery system we will START with. There are two basic
subsets of same—transdermals and injectables. Here are the current
options:
TESTOSTERONE GELS AND CREAMS
The only way to go, in my professional opinion, if physician and
patient prefer a compounded transdermal delivery system. They are easy to
apply, well absorbed, and rapidly establish stable serum androgen
levels (usually by the end of the second day). I recommend all
practitioners first try a testosterone gel for their TRT patients.
Much is made of the risk posed by accidental transferal of
testosterone to others, such as children or sexual partners. Simply
covering with a T-shirt has been shown to block transfer of the
hormone. The testosterone sinks into the skin within an hour, which
acts as the actual reservoir for the hormone's delivery. One may
then shower, or even swim, without worry. I remind my patients that
most of us have neither the time, nor the opportunity, for romance
until evening (given the recommended early morning application), and
a quick shower is always nice to "freshen up" then anyway.
Gels and creams, like all transdermal delivery systems, provide a
bigger boost in DHT levels, compared to injectable testosterone
preparations. This can be a double-edged sword. As DHT is
responsible for all the things of manhood, the transdermals are
better at treating ED than the injectables. However, issues of hair
loss and possible prostate morbidity (a contentiously debatable
point, to be sure) then come into play. Either way, please make sure
to monitor DHT with the transdermals. I'm just not comfortable with
gross elevations in DHT, and prefer to avoid adding finasteride
whenever possible.
Some have reported an increase in hair growth over the application
area(s). All physicians who administer TRT must be prepared to
disappoint their patients at this time by pointing out, sadly, this
same effect cannot be achieved on the scalp.
TESTOSTERONE PATCHES
These can be quite effective, but are inconvenient to use.
Approaching 2/3's of your patients will develop a contact dermatitis
from them at some point. Another drawback is that some patients
report they are constantly aware of their placement, and the patches
are embarrassingly obvious to other gentlemen in certain public
places, such as in the locker room.
The scrotal application variety is the most inconvenient. To see
what I would be putting my patients through, I tried them. After
just a couple days, I'd had more than enough. Men do not generally
enjoy shaving their scrotum, and the patches just do not stay on
well anyway. Applying a hair dryer to the patch, as they must be
warmed first, is also an annoyance. If you go to the gym during the
day, they look strange affixed to the genitals, and must be removed,
then reapplied, to shower. They do not stick well in the first
place, and even less so once they have been reapplied. Of the two
options, I found only the type with the extra adhesive had any
chance of remaining in place. The scrotal variety causes the largest
increases in DHT—which can be good or bad, as previously explained.
TESTOSTERONE PELLETS
In my opinion, their use is absolutely Stone Age. Sure, they can
provide extra revenue by virtue of a billable office based
procedure. However, needlessly exposing patients to the risks ALL
surgeries pose—hemorrhage and infection—is unwarranted. And the area
of insertion will be much tenderer than that following a mere IM
injection. But the real issue which selects against pellet
implantation is concerned with dosing. Let's say you establish
a "usual" initial dose for the pellets. As will be described in the
next section, there is absolutely no way to predict, up front, how a
patient will react to a given dose of testosterone, regardless of
the delivery system. So you bury these pellets in your patient's
backside, and (hopefully) draw follow-up labs in a month or so. What
are you to do if the total testosterone ends up greatly exceeding
the top of normal range (meaning the patient hyper-responded to the
treatment)? Now you must make a much wider incision to remove them,
or a portion of them (and who knows how many to take out?). With
their very long half-life, SOMETHING must be done, lest you risk
actually damaging the health of the patient by elevating
testosterone levels into what might be considered a bodybuilding
steroid cycle. And what if the pellets do not elevate T enough? You
must bring them back in to implant more, and it's difficult to sell
them on this idea, since they probably are not yet feeling the
advantages of TRT enough yet to motivate them into undergoing
another surgical procedure. It just doesn't make sense, to my way of
thinking.
Testosterone pellets do have some benefit in that selected patients
may believe it more convenient to come in every month or six weeks,
and then be done with it for a while. Also, because they release T
in a slow, steady rate, the pellets are less likely to induce
increases in aromatase activity.
TESTOSTERONE INJECTION
I'll start out by describing the drawbacks of IM testosterone. They
are inconvenient for patients who do not wish to give themselves
their own injections, as they must then make weekly trips to your
office for same. Why IM test MUST be dosed weekly will be described
in detail in another section. Some patients, as you well know, just
hate shots (although I have noticed several who had initially
claimed this, but admitted, once they had come to enjoy the benefits
of TRT, actually came to look forward to their weekly injection).
And no doubt, an invasive delivery system brings more risk than, for
instance, a testosterone gel or cream (the other best choice for
TRT).
When considering dosing of testosterone cypionate, it is important
to remember that, due to the weight of the cypionate ester, a 100mg
injection delivers, at best, 70mg of testosterone. This is important
to keep in mind when comparing the effects of a 100mg weekly
injection of test cyp to the 35mg total dose provided by Androgel
5gms QD over the same period.
If low testosterone, start with
HCG
Many practitioners consider this incredible hormone treatment of
choice for hypogonadotrophic (secondary) hypogonadism. Such certainly makes sense, as supplementing with a LH analog indeed increases testosterone production in patients who do not concurrently suffer primary hypogonadism. But often, upwards of 1000IU per day must be given to achieve the desired serum T level. Even then, for some unexplained reason, while serum T levels may be adequately elevated, the patients simply do not report realization of the benefits of TRT, when HCG is administered as sole TRT. You also run the risk of inducing LH insensitivity at that dosage, and therefore may actually cause primary hypogonadism while attempting to treat secondary hypogonadism. HCG, especially at higher doses, also dramatically increases aromatase activity, thus inappropriately elevating estrogens.
 Personally, I recommend never giving more than 500IU of HCG at a time.* %%% Gine2D, I think they have changed this to 250u every other day now.%%%
A real benefit of HCG is that it will prevent testicular atrophy. I do not think we should ignore the aesthetics of that consideration. Your patients will feel the same way.
OTHER MEDICATIONS
I occasionally hear of physicians trying to use a SERM (Selective
Estrogen Receptor Modulator) such as Clomid or Nolvadex, or even an
Aromatase Inhibitor (AI), such as Arimidex, as sole "TRT". All have
been shown to elevate LH, and therefore Total Testosterone levels.
However, patients report no long-term subjective benefits from these
strategies, and the studies thus far reported no long-term changes
in lean body mass, fatigue levels, libido, etc. An added risk of
using an AI is of driving estrogen levels too low, with deleterious
consequences for the lipid profile, calcium deposition, libido, etc.
Finally, Deca-Durabolin (Nandrolone) has no place in TRT. It has a
nasty side effect profile, including uncontrollable progesterone-
like effects (including gynocomastia) and risk of long-term
impotence.
THE MEAT AND POTATOES OF TRT
Now we will delve into the general strategy for administering TRT.
The decision is made, TOGETHER with the patient, which of the
various testosterone delivery systems is to be tried first. Be
prepared to make adjustments, and try other application methods. You
just don't know which will be best for each particular patient until
you try. Besides the simple fact the patient may have a personal
preference, or a logistical consideration (i.e.
inability/unwillingness to self-inject) for a given application,
every-body reacts differently to hormonal manipulation. Some hyper-
respond to a given initial dose, others show hardly any bump in
serum T levels on same. Yet when you switch to a different delivery
system, on initial dosing, they may convert to supraphysiological
androgen levels. The same is true of the subjective benefits from
TRT. I have patients who love testosterone gel because it
successfully treated their ED (the expected outcome because of
dramatically increased DHT production), others get more from IM
testosterone cypionate. My experience thus far has taught me two
lessons: (1) You don't know how a patient will react to a given
dose/system until you try and (2) NOTHING surprises me anymore.
There simply is no way to predict how a particular patient will
respond—not Medical History (i.e. number or severity of symptoms),
body weight, baseline hormone levels, even anabolic steroid history.
I have had very slight gentlemen barely elevate on 100mg of test cyp
per week, and massively muscled former steroid athletes who went to
nearly two times the top of "normal" range on the same dosage (they
had similar baselines). Likewise, one man may see only a modest
increase in DHT on 5gms of Androgel, another may become quite
supraphysiological on same.
I start my guys out on either testosterone cream/gel 5mgs QD or
testosterone cypionate 100mg per week. The IM test cyp must be
administered in weekly injections, as opposed to taking twice the
dosage every other week. Some physicians even dose every third or
fourth week, producing wide swings in serum androgen levels. This
puts the patient on an emotional roller coaster, increases the risk
of developing polycythemia, greatly accentuates aromatase activity,
and actually leaves them lower than they were when they started for
the last half of the cycle. In order to get the serum androgen
concentration to a stable level more quickly, I "frontload" 200mg
the first injection (unless converting over from a gel/cream).
No other medications which manipulate hormone levels are provided
until follow-up labs are returned. For IM test cyp patients, the
second panel is run following the fifth injection. I also keep in
mind the coordination of the injection with the lab draw, as peak
serum levels are attained at about the 48 hour point, then fall to
about 35% at the one week point. However, by the end of the fifth
week, the pharmacodynamics of testosterone cypionate (half life is 5-
8 days) are such that relatively stable serum levels are now being
produced via weekly injections.
Transdermals can be rechecked in two weeks. They produce stable
serum levels, as previously mentioned, for most by the end of the
second or third day. Logistically, it makes sense to send the
patient for follow-up labs after a fortnight, as there is then time
to get the labs back, and bring the patient in, before the initial
30-day supply of the medication runs out. This is better if an
adjustment in dosage is mandated by the follow-up labs, or to
convert to IM dosing should the patient produce too much DHT. It
would be a shame to have the patient refill a script for 5gms of
Androgel, when they, by their labs, are going to have their dosage
reduced to 2.5gms per day because they hyper-responded to the
initial dose, or waste money when what they reallyneed is to be
converted to test cyp.
The question of which testosterone delivery system is to be tried
first (IM or transdermal) is one which brings much confusion amongst
beginning practitioners of TRT. I would, when possible, always start
out a patient on a testosterone cream or gel. Ease of application,
avoidance of intrusion by injection, and increased probability of
successful ED treatment make this so. Also, stable serum levels are
attained quickly, determination of successful treatment is more
forthcoming (although the manufacturer of this product recommends at
least a couple months as adequate trial of therapy). If the labs AND
patient's answers to follow-up subjective report lead to a change to
IM testosterone, the conversion is an easy one to make. Simply apply
the gel, give the shot, then D/C the gel. However, if a patient is
started out on IM test cyp, for instance, yet the patient still does
not feel "right" (and thus you may want to try a transdermal
delivery system to better raise DHT levels), how are you, given the
pharmacodynamics of the testosterone ester, going to safely and
successfully dose the conversion to a transdermal?
Dosing changes are made, TOGETHER with the patient, once follow-up
labwork is back AND the patient is interviewed regarding their
subjective reports of changes in libido, sexual performance,
fatigue, strength, mental outlook, etc. Often they will tell you
they felt "incredible" the first couple of weeks (and bursting with
libido), but they don't feel quite as good now, but still much
better than before they started the TRT. This is because subjective
findings are the best while serum androgen levels are accelerating.
Adjunctive to this phenomenon is the fact their HPTA was not yet
being suppressed, so their endogenous production was higher then
than it would be by the end of the month. TRT patients are always
HPTA suppressed to greater or lesser degree.
Much weight is placed upon the patient's subjective findings, as
they are not likely to remain compliant in the TRT program unless
they feel noticeably better, irrespective of the less obvious long
term improvements in CV health, bone density, decreased risk of
dementia and cancer, etc. Certainly, if the patient reports they are
quite happy at a Total Testosterone level of 600ng/dL, I feel there
is little reason to increase their dosage. As an Osteopath, I am
loath to provide ANY medication, or increase in dosage, without
proven need. As a practical limit, the top of "normal" range for
Total Testosterone provides a ceiling, more or less, above which we
can expect to find the benefits of TRT beginning to reverse
themselves. Actions following androgen receptor binding dramatically
improve health and happiness as we go from the hypogonadal state to
the top of "normal" range, but beyond that the Lipid Profile and
level of insulin sensitivity, for instance, are damaged.
Changes in IM dosing are made in small increments, as response to
same is not linear. It is convenient and practical to increase, or
decrease IM dosing by 20mg at a time, as this is one "tick mark" on
the side of the syringe (for the 200mg/mL concentration). For
Androgel patients, we are more limited by their provided dosing
whereas we can only either drop down to 2.5gms, or add an extra pack
each day (at which time BID dosing may be considered) to reach the
7.5gm, or even 10gm, per day dose. More flexibility is provided
through compounded products for those committed to employment of
transdermal testosterone delivery systems.
Another risk of jumping the dosage too much is that, should serum
androgen levels greatly exceed the top of "normal" range, the
patient risks becoming "spoiled" at that level. They would then feel
the subjective benefits steroid athletes report, and it would be
difficult to get the patient then to be happy at a more moderate—and
proper—dose. It is likely you would also therefore produce elevated
estrogen activity as well, and further muddy the waters with respect
to how the patient feels—and looks (due to emotional changes and even water retention issues from the elevated estrogen). It is far better to make changes in dosing conservatively.
Once the method and dosing is set, by laboratory assay AND subjective report from the patient, then you may address any side effects due to elevated estrogen levels which have occurred. I do not use an AI initially, even when E2 is elevated, because some
patients will actually see a drop in estrogen over baseline on
follow-up. We would have otherwise added an unnecessary (and
relatively expensive) medication. Should the patient develop
any "nipple issues" secondary to accelerating serum androgen levels
and/or elevated estrogen, you cannot start them on a SERM right away
because doing so will invalidate your estradiol assay at follow-up.
Of note, males can experience said "nipple issues" even while
estrogen levels are within physiological range, due to changes in
hormone levels. A drug of the class SERM is treatment of choice in
this case, until symptoms subside.
Indolplex DIM along with 50mg of Zinc will lower E2 levels.
****
I think that most of this is from Dr J Chisler & Dr E Shippen.
Topic: moving beyond gyne (Read 10181 times)
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