Hrt For Men

History of Hypogonadism & the Progression of Testosterone Replacement Therapy

Male hypogonadism is a condition in which the body does not produce enough testosterone and/or has an impaired ability to produce sperm. The biological and clinical effects of testosterone and its deficiency have been known for hundreds of years. However, the scientific history of testosterone began with the transplantation of testicles into capons, or castrated roosters, by Berthold in 1849. Forty years later, Brown-Sequard, the French physician who first hypothesized the existence of hormones, claimed to have rejuvenated himself at age 72 with injection of a testicular extract from guinea pigs and dogs. It was later shown that this extract was almost entirely devoid of any androgenic hormones, and that benefits from it were an apparent placebo effect. Still, interest in hormones continued to grow, and although muchof the early steroid biochemists work was focused on female hormones, testosterone was synthesized in 1935. In 1944,J.A.M.A. published an article, “The Male Climacteric,” by two internists from Detroit, Carl Heller and Gordon Myers,which showed that some aging men develop symptoms attributable to hypogonadism. Shortly thereafter, testosterone was introduced into the clinical setting for replacement therapy.


“Patients using testosterone should seek medical attention immediately if symptoms of a heart attack or stroke are present such as chest pain, shortness of breath or trouble breathing, weakness in one part or one side of the body, or slurred speech.”

Testosterone is a hormone produced primarily by the testis and has many different effects on the body, in part because in can act as three different hormones. Testosterone can act directly by binding to the androgen receptor, or it can beconverted by the enzyme, 5-alpha reductase, to dihydrotestosterone (DHT), which can bind to a greater degree to theandrogen receptor. Testosterone can also be converted by the aromatase enzyme to estradiol and act as an estrogen, which is required for much of its positive effects on bone, body fat, and sexual function. Functions of testosterone include:

  • Normal growth and development of male sex organs
  • Growth of facial and body hair
  • Increases muscle strength and lean body mass
  • Enhances libido
  • Improves energy level
  • Improves mental alertness
  • Promotes sperm production

Testosterone Related Symptoms
Testosterone Deficiency Testosterone Excess
Fatique Weight Gain Acne
Low Libido Headaches Oily Skin
Erectile Dysfunction Sleep Disturbances Loss of Scalp Hair
Decreased Muscle Tone Apathy Aggression
Memory Lapses Depression Thinning Skin
Decreased Concentration Osteoporosis/Fractures Weight Loss
Muscle or Join Point Sleep Disturbances


Testosterone requires the conversion to estradiol for much of its positive effects on bone. Estradiol, within normal range, also helps to decrease body fat and stimulate normal sexual function in men. Although estrogens are normal hormones that are necessary to men, in some cases, men may experience too much estrogen. In such cases, there are medications available to limit the conversion of testosterone to estradiol.

Estrogen Related Symptoms
Estrogen Excess
Weight Gain Hair Loss Emotional Lability
Breast Development Fluid Retention Irritability/Anxiety
Fatigue Brittle Fingernails

Options for Testosterone Replacement Thereapy

Although testosterone has been available to treat hypogonadism since the late 1930s, the modes of application were far from ideal until recently. Presently, there are a variety of testosterone formulations that give the patient a real choice and can make treatment easier. Some of these options are listed below.

Sublingual RDT

Rapid dissolving tablets (RDTs) that are placed underneath the tongue for the testosterone to beabsorbed sublingually. The tablets typically completely dissolve in less than one minute.

Sublingual Drops

A liquid solution that is administered underneath the tongue for rapid absorption.

Topical Creams/Gels

Typically applied in the morning to the upper arms and shoulders and left there for the testosterone to be absorbed through the skin. During the period immediately after application (approx. 15min), skin contact with other persons, especially women and children, should be avoided. Thereafter, the risk of transferring testosterone to other persons is negligible.


Requires minor surgery for subcutaneous insertion (beneath skin), often causing temporary local irritation. Typically, multiple pellets are inserted at one time, however, they are effective for up to half a year.


Depot preparation that has to be injected intramuscularly every week to every four weeks. Often, these injections may be self-administered.

Alternative Treatments

While testosterone is a mainstay in male hormone replacement therapy, alternative treatments exist and may be necessary in order to obtain normal testosterone levels in hypogonadal men. Some of these alternatives are listed below.


A naturally occurring flavone found in passion flowers. Similar to anastrazole, chrysin also inhibits aromatase to help prevent the conversion of testosterone to estradiol, and it is often combined into the same formulation as testosterone. However, all medical literature indicates chrysin is not absorbed via any route of administration.


This medication acts directly on the testes to help stimulate the production of testosterone and sperm.

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