Testosterone is important to both genders

Although testosterone is called the “male sex hormone” and is much higher in men, it is important to both genders: everyone needs it, to support muscle, the heart, personality and libido.

In youth, it is mainly made in the testicles (or ovaries), but in fact, all our cells convert DHEA into testosterone for their own use, 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 and maintains self-confidence, minimising our anxieties and shielding us from depression.

Maximum testosterone production begins at puberty and is approximately 10 times greater in men, than women. In the male, it is responsible for development of the male sex chacteristics; beard and body hair, deepening of the voice by enlargement of the larynx, Increased muscle mass, stronger, heavier bones, Male development of the prostate and the penis and heightened self-confidence.
In the female, testosterone production is insufficient to stimulate male pattern hair growth, hypertrophy of the larynx and other male characteristics; but it is important nevertheless, because it supports self-confidence, self-assurance, cognition and libido.

Male testosterone levels

Serum Testosterone remains high through the third decade, but a gradual fall in production, approximately 1% per year, starts at age 26 in both sexes. In women, the normal serum testosterone at age 20–25 is only 20-30 picomoles per litre, so a 1% loss is easily demonstrated. However a 1%/year downward trend in Testosterone is hard to “see”** in men, because their “normal” blood level spans a wide range, 60–900 pmol/litre and because the male’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.

The testoterone level in the male 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.

Female testosterone levels

Women’s ovaries also produce testosterone in youth, but at menopause they shut down completely. The peripheral cells continue “intracrine” testosterone production***, but the amount made depends on the DHEA supply and so very little gets into the blood. Therefore In post-menopausal women, serum Testosterone tends towards zero, with reduced self-confidence and minimal libido.

In contrast to the male’s experience, reduced testosterone level in the female tends to be symptomatic, especially since it is always associated with DHEA deficiency and often, with intracellular hypothyroidism. The “low testosterone syndrome” (my terminology) in the female most often begins between age 26 and age 30, but can at times be seen by age 20. It usually presents with marked hair loss, brittle fingernails, dry skin, vaginal dryness, reduced self-confidence, low libido and occasionally, “fuzzy thinking”.
This syndrome, often seen in 20-to-30-year-old women, usually responds quickly and well, to oral supplementation of DHEA. * If it does not, investigation for IH should be requested, including TSH, FT4, FT 3 and T3. **

* Childhood PTSD from physical, mental or sexual abuse, often unrecognised, can result in intracellular hypothyroidism and deficiency of DHEA, Testosterone, Progesterone and Allopregnanolone, beginning in the teen years. This is sometimes the reason for depression and obesity in the “troubled teen”. PTSD sets the stage for moderate DHEA/testosterone deficiency, often accompanied by intracellular hypothyroidism and/or progesterone deficiency in the “20s” and severe, symptomatic deficiency by the “30s”.

** 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 and/or sex, as testosterone does 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 mix of “microhormones”. 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.

CAVEAT

For “best practice”, women presenting with hair loss, brittle fingernails and other symptoms reminiscent of hypothyroidism should routinely be investigated with a “thyroid profile“: TSH, free T4, free T3 and reverse T3. If this were done, with correction of the IH (ad hoc), many women would be relieved of the loss of self-image, poor sleep and low-grade depression which reduces the quality of life of so many young women.

EVERYBODY is in the game !

We all, males and females, need, make and use Testosterone, and sooner or later we all become Testosterone deficient. So we all develop some mix of symptoms and/or signs of hypotestosteronemia eventually.
The Baltimore Longitudinal Study of Aging deems the incidence of hypogonadism **** to be 20% in men over 60, 30% in men over 70 and 50% in men over 80 years of age (that may be a little optimistic!).

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

So: what happens in testosterone deficiency?

(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 – low-thyroid symptoms ! – Some are low-Allopregnanolone symptoms !
(All our hormones go down with age, so single-hormone deficiency is rare. We should expect to develop a mixture of low hormone symptoms; but the symptoms of low DHEA do look suspiciously like the symptoms of hypothyroidism – more on that, later).

(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, most of which can are “DHEA-responsive”, can be considered to be reactions of tissues sensitive to Testosterone-deficiency, (or) reduction of Testosterone availability, 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.

in 2010, a small, poorly organized study suggested that testosterone replacement therapy could produce heart attacks. This was not accepted by knowledgeable physicians, but it started a huge argument on the subject. In response to this, the Cleveland clinic decided to do a formal study, in 2015.

The TRAVERSE trial, a randomised, double-blind, placebo-controlled trial, was conducted at 316 clinical-trial sites in the United States and enrolled 5,246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism.

Following is a selection from the report, which I copied from the Cleveland clinic’s article:
“Results showed that among 5,198 patients who received testosterone or placebo for a mean duration of 22 months, testosterone-replacement therapy did not cause more major cardiac events than placebo.
A major cardiac event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group. However, those receiving testosterone did show a higher incidence of atrial fibrillation *, acute kidney injury, and issues arising from blood clots in the veins. Current guidelines recommend that testosterone should be used with caution in men who have had previous blood clots.

* I find this surprising: in my experience, keeping DHEA and testosterone levels up actually protected people from cardiac problems such as fibrillation: see my case history of “Herbert and Herman”.

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 most common in those with low T (look up Dr. Abraham Morgentaler’s many articles on the subject).
In addition, recently (since about 2010) there have been reports of side-effect-free 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 the 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 T to Oestrogen by the liver, with breast enlargement and occasionally, painful and tender breast cysts.
(3) Weight gain around internal organs and in traditionally female areas (hips and lower abdomen), also caused by aromatization of testosterone, to estradiol.

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: Testosterone absorbed into the blood by the gut passes through the liver first and almost all of it is aromatised to oestrogen.
• (3) Don’t take TRT for the wrong reasons: T should not be used as an anabolic steroid.
• (4) In women, DHEA produces a reliable increase in blood testosterone levels, whether taken by mouth or used as a gel or cream, so testosterone prescription is not necessary.

CAVEAT:
Don’t take drugs (like some anti-breast cancer ones) which reduce “aromatisation” of T to Oestrogen. They work very well to reduce Testosterone-to-Oestrogen conversion, erections are normal and the breast enlargement goes away, but interest in sex (libido) goes away too, totally…… MEN NEED OESTROGEN, TO KEEP THEIR LIBIDO UP !!!!

LOW Testosterone IN WOMEN: TRT in the FEMALE

Hypotestosteronemia is a much greater personal, psychogical and social problem for women than it is for men. It starts at a younger age (often before age 26) and is a problem for many women. In women, the loss of libido is profound, associated vaginal dryness and reduced orgasms are more disruptive and the psychological effects, for example 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 testosterone, the female responds to DHEA with a large increase in testosterone 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 it. TRT as such is therefore unnecessary for women.

DHEA replacement therapy for women

The medical literature contains many many articles on the subject, which variously conclude that the best dose of DHEA for a female is, depending on the reporter, between 10 and 100 mg per day. Most of these articles however are predicated on short-term trials (3 months, 6 months, perhaps a year).

What I found in practice, by prescribing DHEA supplementation for Testosterone deficient women, between 2006 and 2021 is that most T–deficient women do very well with 50 mg of DHEA per day. The usual women’s dose of DHEA is 50mg, reduced to 25 mg if side effects ensue.
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.
There is no objection to increasing the dose if necessary and there is no need to worry about elevated blood levels of DHEA: much more important are the testosterone level and how the patient feels.

Testosterone side effects in women, from either Testosterone 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: almost all women benefit from DHEA, in terms of an increase in their libido.
The increase in testosterone level, with resulting improvement in libido, increases as the dosage of DHEA goes up.
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 aggressive personalities before starting DHEA, ran into this problem as their testosterone rose.
(4) Very seldom, scalp hair loss can result from taking T or DHEA. This is due to the T being converted into “DHT” (DiHydroTestosterone), a natural form of Testosterone, which causes hair loss in men.

ADDENDUM

Regarding prostate cancer and Testosterone &/or DHEA (a case report):
In March, 2011 A patient of mine had a rising PSA and a biopsy showed a (Gleason 6) prostate cancer. after complete discussion between myself, the patient and his son, they accepted my explanation and he agreed to try taking DHEA.

He 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.

in 2021, he was unable to urinate because of his enlarging prostate and a prostate resection was done, producing a large amount of prostate tissue. No evidence of prostate cancer was found.
Evidently, taking DHEA cured the prostate cancer in this particular man.

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