Testosterone

Mr T, a DRAKE, symbolising Masculinity & Testosterone
MISTER T

Testosterone

  • Testosterone is the “male sex hormone”. The youthful male generates large quantities in the testicles, while in the female, the ovaries make 10% as much.*
  • Also, in both males and females, all our cells produce testosterone locally, converting DHEA in a process termed “intracrinology” by Professor Fernand Labrie  (1)
  • Testosterone subserves maintenance and repair of muscle, bone, skin, sweat glands and hair; it supports the libido in both male and female. It maintains self-confidence, minimising our anxieties and shielding us from depression.
  • Maximum testosterone production begins at puberty and is responsible for development of the male sex chacteristics; beard hair, deepening of the voice by enlargement of the larynx, building muscle, strengthening bones, growing the prostate and the penis, etc.
  • Serum Testosterone remains high through the third decade, but since it is made from DHEA, a gradual fall in production starts at age 26. (Starting at 26, DHEA production falls 1% per year in both sexes). This is easily demonstrated in women’s blood tests; but a 1%/year downward trend in Testosterone is hard to “see”** in men, because their “normal” blood level spans a wide range (9.2 to 31.8 Nanomoles/L) and because a man’s Testosterone level varies, both with the time of day (highest at 8AM) and with physical and sexual activity.
    Suffice it that although the testicles don’t lose function completely at “andropause”, as the ovaries do at menopause, by age 80 men’s testosterone production is 10-20% of what it was at 25.
    ALSO, to make matters worse, production of “Sex Hormone Binding Globulin” goes up.
    SHBG grabs onto sex hormones and inactivates them!
  • In any case, the testoterone level often doesn’t match up with symptoms: many older men with “low T” are fit, sexually active and cognitively sharp, while many men with mid-normal “T” present to the MD with Low-T problems, even in their 20s.
  • Women’s ovaries also produce testosterone in youth, but only 10% or so of what the testicles do and at menopause they shut down completely. In menopausal women therefore, serum Testosterone tends towards zero. All cells continue “intracrinological” testosterone production***, but the amount made depends on the DHEA supply and so very little gets into the blood.
  • Zero testosterone, plus intracellular hypothyroidism present as hair loss, brittle nails, dry skin, vaginal dryness and low libido, which are often seen in 20-to-30-year-old women. *

* Childhood PTSD from physical, mental or sexual abuse, usually unrecognised, can result in functional hypothyroidism and deficiency of DHEA, Testosterone, Progesterone and Allopregnanolone in the teen years. This is part of the reason for depression and obesity in the “troubled teen”. Further, it sets the stage for moderate deficiency in the third decade and severe, symptomatic deficiency by the fourth.

** The best measure of Testosterone-maufacturing capability is to check the DHEA level, because
– It is the precursor of “T”, so its level gives an accurate measure of possible T production.
– DHEA peaks a little earlier in the morning than testosterone does, but it doesn’t rise and fall with exercise like the testosterone level and therefore “what you see, is what you got”.

*** Our cells have a family of 30 (or so) enzymes, each of which converts DHEA into its own brand of “microhormone”. Each cell type employs its own selection of enzymes to “mix and match” an individual hormone cocktail for its maintenance and repair.
As the DHEA supply falls, all cells begin to suffer from DHEA deficiency, but some parts are more sensitive to “DHEA famine” than others, so the visible and symptomatic effects vary from person to person.

EVERYBODY is in the game !

We all, males and females, need, use and make Testosterone and we all, sooner or later, become Testosterone deficient, so we all develop some mix of symptoms and/or signs of hypotestosteronemia eventually.
The Baltimore Longitudinal Study of Aging reported the incidence of hypogonadism **** as 20% in men over 60, 30% in men over 70 and 50% in men over 80 years of age .

**** I hate the term “Hypogonadism”: the problem is low testosterone, not low gonads !

SO: WHAT HAPPENS IN T DEFICIENSY?

(1) Nuisance-value symptoms:
Low libido
Erectile dysfunction
Fatigue.
Poor motivation
Mood swings
Body and facial hair loss
Difficulty concentrating
Depression
Irritability
Low sense of well-being ………………………….. HEY, WAIT A MINUTE !
Those are stress-related symptoms !
Those are low-DHEA symptoms !
Those are low-thyroid symptoms !
Some are low-Allopregnanolone symptoms !
(All our hormones go down with age, so single-hormone deficiency is rare).

(2) High-grade problems:
Anaemia
Reduced bone mass and increased bone fragility
Reduced muscle mass
Heart “events”
Increased obesity
Cognitive decline

Various syndromes, diseases and illnesses, which can be defined as “DHEA-responsive”, can be considered to be reactions of tissues sensitive to Testosterone-deficiency, (or) reduction of T level below their threshold of need.

Testosterone replacement Therapy

Testosterone replacement therapy (TRT) for men and women with symptomatic deficiency has benefits, such as increased libido and energy level, improved bone density, increased muscle strength and cardioprotective effects: this is well documented.

TRT side effects in the male:

Apart from breast enlargement due to conversion of Testosterone to Oestrogen, by a liver enzyme called “aromatase“, there isn’t much literature on the risks of using testosterone.
It used to be said that TRT can cause worsening of Prostate cancer, but that does not make logical sense, because Prostate cancer is commoner in those with low T.
In addition, recent (since about 2010) there have been reports of TRT in men with cured prostate cancer who need it for sexual dysfunction and in men with really bad prostate cancer, treated with TRT. See addendum at the end of this paper.

There are also reports of association of TRT with polycythemia (red blood cell overproduction which can cause clots), leg swelling, sleep apnoea, heart trouble and liver dysfunction, so those getting TRT should be followed with periodic blood tests to watch for side effects.

However the usual problems with TRT are
(1) “Testosterone high” caused by spiking of T levels in the blood after T injection,
(2) Natural “aromatisation” of the T to Oestrogen by the liver, with breast enlargement and maybe, painful and tender breast cysts.
(3) Weight gain around internal organs and in traditionally female areas (hips, “tummy”).

Avoiding TRT side effects

  • (1) Avoid the “high” with smaller “shots”, given more often, or use gels, patches or implanted tablets instead of injections.
  • (2) Don’t take T by mouth: T absorbed into the blood by the gut into through the liver first and is aromatised to oestrogen.
  • Don’t take TRT for the wrong reasons: T should not be used as an anabolic steroid
  • (3) In women, prescribe DHEA, or use a gel or cream, varying the site so as to avoid hair growth.
  • CAVEAT: Don’t take drugs (like some anti-breast cancer ones) which reduce “aromatisation” of T to Oestrogen. They work very well to reduce T-to-O conversion, erections are normal and the big breasts go away, but interest in sex (libido) goes away too, totally.
    MEN NEED OESTROGEN, TO KEEP THEIR LIBIDO UP !!!!
LOW T IN WOMEN: TRT in the FEMALE

Hypotestosteronemia is a much greater personal, psychogical and social problem for the female than it is for the male. It starts at a younger age (often by age 26) and is much more prevalent.
The loss of libido is more profound, associated vaginal dryness and reduced orgasms are more disruptive and the psychological effects, like reduced self-confidence, can be devastating. This is especially true when low Testosterone is combined with menstrual cycle dysfunction, plus PMDD due to low Progesterone & Allopregnanolone. (2)

Fortunately, whereas in the male DHEA supplementation results in a large increase in serum Oestrogen and only a small “uptick” in T, the female responds to DHEA with a large increase in T and only a slight rise in Oestrogen.
Correction of low T in the female is therefore easily acheived with DHEA.
DHEA supplementation is simple, straightforward, reliable and problem-free, except for the few people who get Testosterone side effects when taking DHEA.

The usual dose of DHEA for a woman is 50mg daily, reduced to 25 mg if she gets side effects.
However infertility clinics routinely prescribe 75mg per day and in my practice I knew of three women who insisted that they needed 100mg every morning, so there is no objection to increasing the dose if necessary.

Testosterone side effects in women, from either T or DHEA

(1) Occasionally an increase in facial hair, development of acne and an increased oiliness of the skin is seen. The problem is usually dose-dependent, stopping when the strength of the supplement is reduced.
(2) Increased libido: only two women in my 15 years of practice complained of excessive libido: interestingly, one of these was in her 70s (!).
(3) Increased aggressiveness and anger: a few of my patients, who had been aggressive types before starting DHEA, ran into this problem.
(4) Very seldom, scalp hair loss can result from taking T or DHEA. This is due to the T being converted into “DHT” (DiHydroTestosterone).
DHT is a natural form of T, which causes hair loss in men.

ADDENDUM

Regarding prostate cancer and Testosterone &/or DHEA:
In March, 2011 A patient of mine had a rising PSA and a biopsy showed a (Gleason 6) prostate cancer. He agreed to try taking DHEA and took it until Dec, 2012. In Dec 2012 ultrasound did not show a cancer and no biopsy was done.
A biopsy in July, 2014 showed suspicious cells only and a final biopsy in Dec 2014 was negative for cancer.

Lady T, the drake's  mate, symbolising  importance of Testosterone to the female
LADY Testosterone
REFERENCES

(1) Bipolar AndrogenTherapy: The Rationale for Rapid Cycling of Supraphysiologic Androgen/Ablation in Men With Castration Resistant Prostate Cancer, By Samuel R. Denmeade* and John T. Isaacs, in Prostate. 2010 Oct 1; 70(14): 1600–1607. doi: 10.1002/pros.21196 .

(2) Effect of bipolar androgen therapy for asymptomatic men with castration-resistant prostate cancer: results from a pilot clinical study ‘Bipolar’ therapy:
By Michael T Schweizer  1 Emmanuel S Antonarakis  2 Hao Wang  2 A Seun Ajiboye  2 Avery Spitz  2 Haiyi Cao  2 Jun Luo  2 Michael C Haffner  2 Srinivasan Yegnasubramanian  2 Michael A Carducci  2 Mario A Eisenberger  2 John T Isaacs  2 Samuel R Denmeade  1, Sci Transl. Med. 7 269ra2 (2015). https://pubmed.ncbi.nlm.nih.gov/25568070/

(3) Bipolar androgen therapy sensitizes castration-resistant prostate cancer to subsequent androgen receptor ablative therapy. By Laura A.SenaHaoWangSu J.Lim ScMIrinaRifkindNdukuNgombaJohn .Isaacs JunLuo CarolinePratz VictoriaSinibaldi Michael A.Carducci Channing J.Paller Mario A.Eisenberger Mark C.Markowski Emmanuel S.Antonarakis Samuel R.Denmeade

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