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Testimonial – Triumphs and Tragedies of an Anabolic Steroid User, Part 1

by Austin Knight

Editor’s Note: This is the first installment of a three part series by an anabolic steroid user. In order to give real facts of what happens to users who take steroids, Steroidology feels compelled to give a voice to users who have experienced first hand the positive and negative effects of these drugs.

In this article, I will detail my journey with anabolic steroids and how they have impacted my life. The purpose of this multi-series article is to share my experiences over an 18 year span, in hopes that my experiences become educational. steroid user

I was 18 years old when I realized that my progress at the gym was unsatisfactory. The extent of my research with respect to growth was reading a book and renting some bodybuilding related VHS tapes. The motivation from the little research I had done faded away fairly quickly. It was quite frustrating as I watched several gym goers develop much larger physiques than myself.  “They have to be using steroids.” I said to myself. Without a second thought, I made the decision to find and use steroids.

A few weeks pass by and through networking, I managed to get ahold of a few Boldenone (EQ) vials and Sustanon (a mix of testosterone esters). I was 19 years old at this stage. The seller instructed me to inject 2 CC of each compound once weekly. I asked if I should be worried about any adverse reactions, to which he responded, “No, you’ll be fine”.

I followed his lead and started my first cycle that very evening. Adrenaline, placebo and excitement all fueled my body and mind from the very moment I pulled the needle out of my deltoid. I immediately headed over to the gym for one of my most intense workout sessions ever. I continued with my injection protocol while counting the days and minutes for the day the steroids “kick in.” Disappointment began to settle in around the sixth week when I realized I was not seeing much progress but I still continued with my protocol.

I complained to a few fellow steroid users about my progress and was told that I needed to “eat like a horse.” Following their advice, I started eating anything and everything that came my way. Sure enough, two weeks of eating this way had me showing development and growth. I was excited again and began to eat even more. I grew from a mere 170 lbs to a whopping 195 lbs. I felt great, larger than life and invincible. I did not want to stop my cycle but was told I needed to in order for progress to continue. I was advised to taper off my doses for two weeks. Tapering off the steroids was the “Post Cycle Therapy” ideology at my gym in the mid 90’s.

With my confidence through the roof, I managed to go out on more dates and meet more people. I was never antisocial, but I was on a different level after this cycle. One of those nights while at home with an ex-girlfriend, I stepped out of bed and headed to the restroom. This is when I heard her say “Oh My God”! I thought she was complimenting me, only to find out she was pointing at my back. I turn my head back towards the mirror only to be completely shocked. My back was covered in darkened/brown spots. Some small, some large. I was confused, embarrassed and angry.

post hyperpigmentaion

A back with a very light case of post hyperpigmentation. The spots caused by this skin disorder can be much larger.

I knew it must have had to do with the steroids that I was using. The following day I visited a dermatologist. I did not mention any steroids use in fear of repercussions at the time. I was far from savvy with respect to blood work, but several panels were ordered. The dermatologist was concerned because it suddenly appeared, which is indicative of recent either events or drug intake. It wasn’t too long before I was called in and asked if I used steroids. Apparently my blood work indicated elevated serum testosterone and estradiol. While admitting use is not acceptable in my book today, at the time it seemed appropriate as I wanted a solution for my problem. I was young, and only a solution mattered to me at the time.

The diagnosis that was given to me was Post Hyperpigmentation. This is a condition where acne spots damage the skin, causing it to discolor permanently. While I did experience some acne, it certainly was not as saturated as these darkened spots on my back. Some of which are over 3 inches in diameter. I was not satisfied with the diagnosis and decided to research this on my own. I did however, accept several prescription medications in both forms; oral and transdermal. None of which made a difference.

Over the next year the pigmentation continued to develop, saturating my shoulders and finally stopping at my deltoids. My years of research did not lead to a cure, but certainly indicated that excessive hormonal fluctuation was the cause. Anabolic steroids put my body’s melanin production into overdrive, leaving me with permanent pigmentation. There is no cure. I can only attempt to lighten the spots. This has also proven ineffective as skin lightening does not discriminate to surrounding areas. So while the pigmentation may be slightly lighter, the normal skin is slightly lighter than natural as well. I’m unable to even the ratio.

This is quite frustrating for me. I like to believe that I am a hard worker, a determined weight lifter and have sculpted an above average body. My current statistics are 6.0 ft. tall, 228 lbs at 11% body fat. I’ve been much heavier and much lighter. My current state is quite near to my final goal of 235 lbs at 10% body fat. Unfortunately, I don’t feel comfortable taking my shirt off at the beach, although I am confident (from what I see) that my body shows that harder work has been put in than others roaming the beach.

Sadly, this is the very beginning of my side effects. More issues arise as my body worsens with other imperfections and lifelong defects. Stay tuned for a follow up article as you follow me through this journey.

Part 2

Anabolic steroids can lead to higher Hematocrit levels which can lead to high blood pressure and excessive thickening of the blood.

Elevated Hematocrit: The Hidden Danger of Anabolic Steroid Use

Many users of anabolic steroids – ranging from those using moderate doses of Testosterone for Hormone Replacement Therapy, athletes hoping to gain a competitive edge, professional bodybuilders hoping to gain muscle, and the everyday exercise enthusiast hoping to look good on the beach – are all very aware of the potential for these drugs to induce severe side effects such as Hypogonadism (reduced testicular function), Gynecomastia (breast tissue growth in males), and HyperCholesterolemia (High Cholesterol).

Several types of drugs are used to prevent some of these issues –  Nolvadex, to prevent breast growth, Statin drugs to address cholesterol issues, and the use of HCG (human chorionic gonadotropin) to increase testicular production of Testosterone. These drugs still fall short of completely eliminating the risk of using excessive amounts of hormones for extended periods of time, so users attempt to limit the use, both in dosage and in cycle length, in order to avoid these short comings. Even with all of this preparation, it is absolutely crucial for anyone using steroids to consider one very important, unavoidable side effect of anabolic use, and one that is silent, only detectable during blood tests, and can cause severe physical health problems, including heart attack, stroke and even death.

picture of Anabolic steroids can lead to higher Hematocrit levels which can lead to high blood pressure and excessive thickening of the blood.

Anabolic steroids can lead to higher Hematocrit levels which can lead to high blood pressure and excessive thickening of the blood.

Anabolic steroids increase red blood cells, which leads to an increase in the amount of oxygen that can be delivered to muscle. This adds a certain athletic advantage. If left unchecked, however, Hematocrit levels (the name for the test used to determine the amount of red blood cells present in blood plasma) can reach dangerous levels, causing elevated blood pressure, and increasing blood thickness, which can lead to disruption of blood flow in major arteries and vessels, leading to heart attack and stroke.

One steroid, known as Equipoise, or Boldenone Undecylenate, has gained a particular reputation for increasing Hematocrit much more than other steroids. While this is true to a certain extent, it is clearly established that all androgenic/anabolic hormones increase RBC( red blood cell count). Even the “safer” steroids such as Anavar have a strong proclivity towards raising Hematocrit.

In order to monitor one’s health, a regular blood work panel must be done at least once every quarter year. In addition to hormone levels, cholesterol, glucose tolerance and blood pressure, one must also measure Hematocrit to ensure that levels have not reached a dangerously excessive amount. In adult males, a normal range for Hematocrit will be between 42% to 54%. Anything above 54% is an indicator of potential cardiovascular and circulation damage. In women, although anabolic steroids will always be ill-advised for this part of the human population, the numbers are even lower – 38% to 46%.

So what steps should a user take when they discover they have high hematocrit? First and foremost you should be working closely with your doctor to monitor these numbers and he or she will have your next step planned should you find these numbers climbing above the safe range. For those users who still continue to neglect to work with a physician while monitoring their hormones, it is essential to stop the use of the hormones immediately. If one is permanently on hormones, as in the case of HRT, it may be necessary to lower the dosage to no more than 100mg per week of a long estered hormone such as Testosterone Cypionate. If Hematocrit is reaching above 59%, it will be necessary to undergo phlebotomy treatments, where excess blood is drained, which allows Hematocrit levels to return to normal. When levels reach unsafe numbers, most blood donation centers will refuse to allow users to donate. Whatever the case may be, high Hematocrit levels are an issue that must be addressed as soon as possible, by eliminating the offending agent, and finding a way to quickly reduce blood volume.

A few very important things to keep in mind while maintaining a healthy Hematocrit level. Maintaining hydration is essential. A dehydrated athlete will quickly increase the thickness of the blood, and the percentage will go up considerably. Always maintain proper hydration. If you exercise frequently, make sure you consume even more water than is normally recommended for average individuals. Naringin, a component of grapefruit, has been shown in studies to reduce excessive hematocrit, while at the same time having no effect on those with healthy Hematocrit levels. The only drawback to this option is that Naringin inhibits a class of enzymes in the liver known as CYP450. This can cause very high levels of certain medications that are normally broken down in the liver by this enzyme. While the idea might seem appealing, to increase levels of a hormone or fat burning drug, for instance, the truth is there are great consequences to inhibiting this enzyme and can cause physical harm. Of course, the last and final way to ensure you are maintaining proper Hematocrit levels is to abstain from using anabolic steroids. If, however, you decide to use these substances please understand that the greatest risk comes in higher dosages, used for extended periods of time. Many modern users of anabolic steroids have come to believe they are exempt from risk factors to their health by continuing to use high doses of androgens without any intended break at any point. They falsely assume that they have all of their bases covered by utilizing ancillary drugs to control other side effects. Unfortunately this is not the case, and certainly one of the biggest concerns to your health is elevated Hematocrit.



Short-term side effects of steroid use

picture of man with steroidacne

Acne is a common side effect of steroid use.

Anabolic steroids are a synthetic form of the male hormones testosterone and dihydrotestosterone.  There are numerous reasons people choose to use steroids but it usually boils down to two basic reasons, increased performance and a better self image.  They are most frequently used by athletes and body builders to improve their size, strength, speed and stamina.  Whatever the users goal they tend to overlook the seriousness of the potential risks.  In recent studies done by the National Institute of Drug
Abuse indicates that there are at least 325,000 teenage boys and 175,000 teenage girls that admit to using steroids.
Most users, especially teenagers will tell you that they have educated themselves on the use of anabolic steroids and their side effects, however, most of the time their “education” was provided by someone they know that uses steroids, in other words hear say, or they found sites on the internet that provide limited information at best in order to promote their product.  Also, many users believe that they aren’t taking doses that are harmful because they are “cycling”.  These beliefs are closer to fantasy than reality.  The only way to achieve the results you are seeking is to take massive doses, up to 100 times more than a Dr would prescribe for a medical issue, which makes them extremely dangerous.
There are numerous side effects associated with the use of anabolic steroids both short term and long term.  Some side effects are specific to men others to women and many are experienced by both men and women.  One of the most common side effects is severe acne.  Steroids cause the sebaceous glands in our skin to become enlarged causing glands to increase production of oil which then serves as “food” for bacteria.  Teens experience a normal surge in hormone production called “puberty”.  It is this normal surge that causes teens to develop body hair and deeper voices in boys and acne in both boys and girls and when you add steroids to the mix it’s a recipe for trouble.
Another common side effect that users don’t think about is called testicular atrophy which is the medical term for shrunken balls, and it isn’t only a cosmetic problem.  Normally the brain sends signals to the testes to produce testosterone, however by introducing an outside source of testosterone the brain stops sending those signals so the testes no longer produce their share of testosterone.  In addition to that the outside source of testosterone also causes the brain to slow down sperm production because it believes your body is receiving sperm from another source, usually a needle.  This leads to sterility and many experts believe steroid use causes permanent sterility though there is no proof one way or the other, but is it really worth the risk?
Another very common side effect is called gynecomastia which is the medical term for developing “man-boobs”.  Because most users are taking such high doses there is a significant imbalance of testosterone in your body.  The extra testosterone is then converted into estrogen as well as other female hormones.  when the male body has that much estrogen along with the other female hormones female breast tissue develops causing men to have female appearing breasts.  These “man-boobs” are permanent.  The only treatment is surgical removal of the female breast tissue which includes a long and painful recovery process.  On top of that the cost is prohibitive and it is an out of pocket expense as insurance companies do not cover steroid abuse.
Now lets move on to the cardiac system.  Some side effect will develop sooner than others and some develop only after long term use, whether you  “cycle” or not.  Steroids cause the body to retain extra sodium and water instead of flushing it out.  In addition to sodium and water they increase the red bloods cells and platelet levels.  Individually these factors can lead to high blood pressure, but combined they always lead to high blood pressure and that leads to another whole list of side effects.  For example, the heart gets larger which can lead to heart failure, and/or aneurysms can also develop in numerous blood vessels.  The blood vessels in different organs and areas through out the body narrow and harden especially those in the brain, heart and kidney’s as well as the legs.  This then can lead to other complications varying from heart attacks and strokes to renal failure or sometimes amputation of a leg.  It is also possible for blood vessels in the eyes to burst and can even lead to blindness.
Another vital organ that is significantly affected is the liver.  The liver is as critical to the body’s function as the heart, you can’t live without it.  Liver tumors as well as a condition known as peliosis hepatitis have been linked to steroid use.  Peliosis hepatitis is a condition in which blood filled cysts develop in the liver.  These tumors and cysts can burst and cause internal bleeding and these are the short term effects so imagine what the long term effects are.
Then it’s time to move on to the prostate gland.  An enlarged prostate gland is rarely seen in young men unless they are using steroid.  The male prostate gland grows to 30 times it’s original size naturally over the average life span, add steroids to that and  in no time your prostate gland is the size of a grapefruit.
Women also suffer from baldness because the body over produces a hair inhibitor enzyme known as DHT.  Women also develop certain normally male characteristics like growing facial hair, increased body hair with coarse skin as well as a deeper male sounding voice.  Women also experience the same damage to their organs including the heart, brain, liver and kidney’s as men do.
These are the most common side effects that can develop after using steroids for a short time, some are permanent while other resolve after steroid use is stopped and with treatment if caught soon enough.  There are also effects that develop after long term steroid use as well as psychological effects that can significantly impact your life.


Pitfalls of steroid use

picture of steroids in olympic

steroids in olympic

Steroids make the news quite often, but with the Olympic Games here again steroids and “doping” are back in the headlines.  When a young girl from China, which happens to be one of the countries with a history of steroid use by it’s athletes, is able to beat Ryan Lochte’s record everyone wants to know how she did it.
What makes the Olympics different than other major sporting events is that they are watched by nearly everyone in every country, young and old over a 2 week period.  During these 2 weeks kids and teens see thousands of ‘buff” athletes and think “I want to be like that”.  Some of these kids will look to steroids to help them along.  The problem with steroids is not only are they illegal they can have serious and dangerous side effects.  Steroids fall into 2 categories, anabolic steroids and corticosteoids.  Both have significant medicinal value as well as significant side effects.  Anabolic steroids or AAS’s are the type used by athletes and body builders for their muscle building and masculine properties.  The thing that makes them so potentially dangerous is that in order for them to be effective for those purposes they need to be taken in doses 10 to 100 times higher than the highest therapeutic dos given for treatment of a medical condition.  Taking any medication 10 to 100 times the normal therapeutic dose significantly increases your chances of experiencing side effects.  So before you consider using steroids to accomplish your goal you need to think about the potential consequences.  First of all if your goal is to become an Olympian or a professional athlete steroids are illegal and you will be tested.  If you are considering steroids for other reasons you need to carefully research the steroids you are considering and know the potential side effects.
One of the things that makes steroid use so dangerous is that many of the users take a combination of several different types of AAS’s and non-steroidal supplements to get the maximum effect.  Long term steroid use affects several chemicals and pathways in the brain including serotonin and dopamine which have a significant effect on our moods and behavior.  So while most steroid users say they feel good even great while taking steroids there are also severe mood swings that occur.  These mood swings can become viiolent, known as “roid rage” as well  as lead to paranoia, and delusions.  Though steroids don’t become addictive in the same sense as a heroine user the body does develop a resistance requiring more and more of the drug to achieve the same effect.  For this reason many steroid users will take them in an on – off cycle, taking them for a period of time then stopping for a period of time before starting again.
Long term steroid use/abuse can cause serious, irreversible health conditions as well including kidney failure, liver damage, and numerous cardiovascular problems like high blood pressure and enlargement of the heart and increase your risk of heart attack and stroke for all ages.  That includes teens and young adults.  There are also many side effects that may not be life threatening but also need to be considered if you are considering steroid use.  In men that take steroids those would include a decreased sperm count and/or infertility so if you’re thinking about having children you need to take this into consideration.  There is also an increased chance of developing prostate cancer.  Men using steroids also tend to develop alopecia or baldness as well as breasts known as gynecomastia.  Women that take AAS’s tend to develop male characteristics including facial hair and a deeper voice, they can also develop whats known as male pattern baldness.  Women taking steroids will also usually notice changes or even cessation of their menstrual cycle.  adolescents tend to have impaired growth, not attaining their expected height as well as accelerated puberty changes.  If all that isn’t enough, for those users that use injectable steroids there’s also the risk of either contracting or giving hepatitis and HIV/AIDS.
If you are still thinking about trying steroids like it or not you reallu need to see your Dr for a complete physical.  It’s important to know if you have any previously unknown health issues before beginning a steroid regime.  Then research, research, research!   Become informed, know what you’re taking and what to watch for.

Gynecomastia: Etiology, Diagnosis, And Treatment

by H. Hajdo Everything you need to know about gyno.BREAST DEVELOPMENT

Male breast development occurs in an analogous fashion to female breast development. At puberty in the female breast, complex hormonal interplay occurs resulting in growth and maturation of the adult female breast.

In early fetal life, epithelial cells, derived from the epidermis of the area programmed to later become the areola, proliferate into ducts, which connect to the nipple at the skin’s surface. The blind ends of these ducts bud to form alveolar structures in later gestation. With the decline in fetal prolactin, placental estrogen and progesterone at birth, the infantile breast regresses until puberty (13).

During thelarche, the initial clinical appearance of the breast bud, growth and division of the ducts occur, eventually giving rise to club-shaped terminal end buds, which then form alveolar buds. Approximately a dozen alveolar buds will cluster around a terminal duct, forming the type 1 lobule. Eventually, the type 1 lobule will mature into types 2 and 3 lobules, called ductules, by increasing its number of alveolar buds to as many as 50 in type 2 and 80 in type 3 lobules. The entire differentiation process takes years after the onset of puberty and, if pregnancy is not achieved, may never be completed (38).


The initiation and progression of breast development involves a coordinated effort of pituitary and ovarian hormones, as well as local mediators (see Figure).

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Estrogen and progesterone act in an integrative fashion to stimulate normal adult female breast development. Estrogen, acting through its ER a receptor, promotes duct growth, while progesterone, also acting through its receptor (PR), supports alveolar development (13). This is demonstrated by experiments in ER a knockout mice which display grossly impaired ductal development, whereas the PR knockout mice possess significant ductal development, but lack alveolar differentiation (25,6).

Although estrogens and progestogens are vital to mammary growth, they are ineffective in the absence of anterior pituitary hormones (13). Thus, neither estrogen alone nor estrogen plus progesterone can sustain breast development without other mediators, such as GH and IGF-1, as confirmed by studies involving the administration of estrogen and GH to hypophysectomized and oophorectomized female rats, which resulted in breast ductal development. The GH effects on ductal growth are mediated through stimulation of IGF-1. This is demonstrated by studies of estrogen and GH administration to IGF-1 knockout rats that showed significantly decreased mammary development when compared to age-matched IGF-1- intact controls. Combined estrogen and IGF-1 treatment in these IGF-1 knockout rats restored mammary growth. (21, 36). In addition, Walden et al. demonstrated that GH-stimulated production of IGF-1 mRNA in the mammary gland itself, suggesting that IGF-1 production in the stromal compartment of the mammary gland acts locally to promote breast development (43). Furthermore, other data indicates that estrogen promotes GH secretion and increased GH levels, stimulating the production of IGF-1, which synergizes with estrogen to induce ductal development.

Like estrogen, progesterone has minimal effects in breast development without concomitant anterior pituitary hormones; again indicating that progesterone interacts closely with pituitary hormones. For example, prolonged treatment of dogs with progestogens such as depot medroxyprogesterone acetate or with proligestone caused increased GH and IGF-1 levels, suggesting that progesterone may also have an effect on GH secretion (29). In addition, clinical studies have correlated maximal cell proliferation to specific phases in the female menstrual cycle. For example, maximal proliferation occurs not during the follicular phase when estrogens reach peak levels and progesterone is low (less than 1 ng/mL[3.1nmol}), but rather, it occurs during the luteal phase when progesterone reaches levels of 10-20 ng/mL (31- 62nmol) and estrogen levels are two to three times lower than in the follicular phase (38). Furthermore, immunohistochemical studies of ER and PR showed that the highest percentage of proliferating cells, found almost exclusively in the type 1 lobules, contained the highest percentage of ER and PR positive cells (38). Similarly, there is immunocytological presence of ER, PR, and androgen receptors (AR) in gynecomastia and male breast carcinoma. ER, PR and AR expression was observed in 100% (30/30) of gynecomastia cases (37). Given these data and the fact that PR knockout mice lack alveolar development in breast tissue, it appears as if progesterone, analogous to estrogen, may increase GH secretion and act through its receptor on mammary tissue to enhance breast development, specifically alveolar differentiation (25, 16).

Prolactin is another anterior pituitary hormone integral to breast development. Prolactin is not only secreted by the pituitary gland but may be produced in normal mammary tissue epithelial cells and breast tumors. (39, 23). Prolactin stimulates epithelial cell proliferation only in the presence of estrogen and enhances lobulo-alveolar differentiation only with concomitant progesterone.


Estrogen effects on the breast may be the result of either circulating estradiol levels or locally produced estrogens. Aromatase P450 catalyzes the conversion of the C19 steroids, androstenedione, testosterone, and 16-a-hydroxyandrostenedione to estrone, estradiol-17b and estriol. As such, an overabundance of substrate or an increase in enzyme activity can increase estrogen concentrations and thus initiate the cascade to breast development in females and males. For example, in the more complete forms of androgen insensitivity syndromes in genetically male (XY) patients, excess androgen aromatizes into estrogen resulting in not only gynecomastia, but also a phenotypic female appearance. Furthermore, the biologic effects of over expression of the aromatase enzyme in female and male mice transgenic for the aromatase gene result in increased breast proliferation. In female transgenetics, over expression of aromatase promotes the induction of hyperplastic and dysplastic changes in breast tissue. Over expression of aromatase in male transgenics caused increased mammary growth and histologic changes similar to gynecomastia, an increase in estrogen and progesterone receptors and an increase in downstream growth factors such as TGF-beta and bFGF (15). Thus, although androgens do not stimulate breast development directly, they may do so if they aromatize to estrogen. This occurs in cases of androgen excess or in patients with increased aromatase activity.

PHYSIOLOGIC gynecomastia gynecomastia, breast development in males, can occur normally during three phases of life. The first occurs shortly after birth in both males and females. This is caused by the high levels of estradiol and progesterone produced by the mother during pregnancy, which stimulates newborn breast tissue. It can persist for several weeks after birth and can cause mild breast discharge called "witch's milk" (38).

Puberty marks the second situation in which gynecomastia can occur physiologically. In fact, up to 60% of boys have detectable gynecomastia by age 14. Although it is mostly bilateral, it can occur unilaterally, and usually resolves within 3 years of onset (38). Interestingly, in early puberty, the pituitary gland releases gonadotropins in order to stimulate testicular production of testosterone mostly at nighttime. Estrogens, however, rise throughout the entire day. Some studies have shown that a decreased androgen to estrogen ratio exists in boys with pubertal gynecomastia when compared with boys who do not develop gynecomastia (30). Furthermore, another study showed increased aromatase activity in the skin fibroblasts of boys with gynecomastia. Thus, the mechanism by which pubertal gynecomastia occurs may be due to either decreased production of androgens or increased aromatization of circulating androgens, thus increasing the estrogen to androgen ratio (26).

The third age range in which gynecomastia is frequently seen is during older age (>60 years). Although the exact mechanisms by which this can occur have not been fully elucidated, evidence suggests that it may result from increased peripheral aromatase activity secondary to the increase in total body fat, coupled with mild hypogonadism associated with aging. For instance, investigators have shown increased urinary estrogen levels in obese individuals, and have demonstrated aromatase expression in adipose tissue (32). Thus, like the gynecomastia of obesity, the gynecomastia of aging may partly result from increased aromatase activity, causing increased circulating estrogen levels (7). Moreover, not only does total body fat increase with age, but there may be an increase in aromatase activity in the adipose tissue already present, increasing circulating estrogens even further. Lastly, SHBG increases with age in men. Since SHBG binds estrogen with less affinity than testosterone, the bioavailable estradiol to bioavailable testosterone ratio may increase in the obese older male.


Since the development of breast tissue in males occurs in an analogous manner to that in females, the same hormones that affect female breast tissue can cause gynecomastia. The testes secrete only 6-10 mg of estradiol and 2.5 mg of estrone per day. Since this only comprises a small fraction of estrogens in circulation (i.e. 15% of estradiol and 5% of estrone), the remainder of estrogen in males is derived from the extraglandular aromatization of testosterone and androstenedione to estradiol and estrone, respectively (27). Thus, any cause of estrogen excess from overproduction to peripheral aromatization of androgens can initiate the cascade to breast development.


Testicular tumors can lead to increased blood estrogen levels by: estrogen overproduction; androgen overproduction with aromatization in the periphery to estrogens; and by ectopic secretion of gonadotropins which stimulate otherwise normal Leydig cells. Tumors causing an overproduction of estrogen represent an unusual but important cause of estrogen excess. Examples of estrogen-secreting tumors include: Leydig cell tumors, Sertoli cell tumors, granulosa cell tumors and adrenal tumors.

Interstitial cell tumors, or Leydig cell tumors constitute 1%-3% of all testis tumors. Usually, they occur in men between the ages of 20 and 60, although up to 25% of them occur prepubertally. In prepubertal cases, isosexual precocity, rapid somatic growth, and increased bone age with elevated serum testosterone and urinary 17-ketosteroid levels are the presenting features. In adults, elevated estrogen levels coupled with a palpable testicular mass and gynecomastia may develop. Though mostly benign, Leydig cell tumors may be malignant and metastasize to lung, liver, and retroperitoneal lymph nodes (34, 14).

Sertoli cell tumors comprise less than 1% of all testicular tumors and occur at all ages, but one third have occurred in patients less than 13 years, usually in boys under 6 months of age. Although they arise in young boys, they usually do not produce endocrinologic effects in children. Again, the majority are benign, but up to 10% are malignant. gynecomastia occurs in one third of cases, presumably due to increased estrogen production (34).

Granulosa cell tumors, which occur very rarely in the testes, can also overproduce estrogen. In fact, only eleven cases have been reported with gynecomastia as a presenting feature in half of them (28).

Germ cell tumors are the most common cancer in males between the ages of 15 and 35. They are divided into seminomatous and nonseminomatous subtypes and include embryonal carcinoma, yolk sac carcinoma, choriocarcinoma and teratomas. Elevated alpha fetoprotein (AFP) and b HCG function as reliable markers in some tumors. As a result of the increased b HCG, acting analogously to LH to stimulate the Leydig cell LH receptor, testicular estrogen production is also increased, which, in turn, can cause gynecomastia. Although germ cell tumors generally arise in the testes, they can also originate extra-gonadally, specifically in the mediastinum. These extragonadal tumors also possess the capability of producing b HCG, but they must be differentiated from a multitude of other tumors such as large cell carcinomas of the lung which can synthesize ectopic b HCG (31).

Some neoplasms that overproduce estrogens also possess aromatase overactivity. Sertoli Cell tumors in boys with Peutz-Jegher syndrome, an autosomal dominant disease characterized by pigmented macules on the lips, gastrointestinal polyposis and hormonally active tumors in males and females, for instance, have repeatedly demonstrated aromatase overactivity, resulting in gynecomastia, rapid growth and advanced bone age as presenting features (18, 44, 10). Feminizing Sertoli cell tumors with increased aromatase activity can also be seen in the Carney complex, an autosomal dominant disease characterized by cardiac myxomas, cutaneous pigmentation, adrenal nodules and hypercortisolism. Other than sex-cord tumors, fibrolamellar hepatocellular carcinoma has also been shown to possess ectopic aromatase activity, causing severe gynecomastia in a 17-year-old boy (2). Furthermore, adrenal tumors can secrete excess dehydroepiandrosterone (DHEA), DHEA-sulfate (DHEAS) and androstenedione which can then be aromatized peripherally to estradiol.

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Besides tumors, other conditions have been associated with excessive aromatization of testosterone and androgens to estrogen, which results in gynecomastia. For instance, a familial form of gynecomastia has been discovered, in which affected family members have an elevation of extragonadal aromatase activity (5). As stated, obesity may cause estrogen excess through increased aromatase activity in adipose tissue. Furthermore, hyperthyroidism induces gynecomastia through several mechanisms, including increased aromatase activity (38).


Another cause of gynecomastia from estrogen excess includes steroid displacement from sex-hormone binding globulin (SHBG). SHBG binds androgens more avidly than estrogen. Thus, any condition or drug that can displace steroids from SHBG, will more easily displace estrogen, allowing for higher circulating levels of estrogen. Drugs can cause gynecomastia by numerous mechanisms besides displacement from SHBG. These drugs and their mechanisms will be addressed in a subsequent section.


Breast development requires the presence of estrogen. Androgens, on the other hand oppose the estrogenic effects. Thus, an equilibrium exists between estrogen and androgens in the adult male to prevent growth of breast tissue, whereby either an increase in estrogen or a decrease in androgen can tip the balance toward gynecomastia. Increased estrogen levels will increase glandular proliferation by several mechanisms. These include direct stimulation of glandular tissue and by suppressing LH, therefore decreasing testosterone secretion by the testes and exaggerating the already high estrogen to androgen ratio.

Besides increased estrogen production, decreased testosterone levels can cause an elevation in the estrogen to androgen ratio, producing gynecomastia. Primary hypogonadism, with its reduction in serum testosterone and increased serum LH levels increases testicular estradiol production and is associated with an increased estrogen to androgen ratio. Klinefelter’s syndrome, occurring in 1 in 500 males who possess an XXY karyotype and primary testicular failure, features gynecomastia as well, again presumably secondary to decreased testosterone production, compensatory increased LH secretion, overstimulation of the Leydig cells and relative estrogen excess. In addition, any acquired testicular disease resulting in primary hypogonadism such as viral and bacterial orchitis, trauma, or radiation can also promote gynecomastia by the same mechanisms (27). Lastly, enzyme deficiencies in the testosterone synthesis pathway from cholesterol also result in depressed testosterone levels and hence a relative increase in estrogen. Deficiency of 17-oxosteroid reductase, the enzyme that catalyzes the conversion of androstenedione to testosterone and estrone and estrone to estradiol, for example, will cause elevation in estrone and androstenedione, which is then further aromatized to estradiol (7).

Secondary hypogonadism, if severe enough, results in low serum testosterone and unopposed estrogen effect from increased conversion of adrenal precursors to estrogens (27). Thus, patients with Kallmann’s syndrome, a form of congenital secondary hypogonadism with anosmia, also develop gynecomastia. In fact, hypogonadism from whatever cause constitutes most cases of gynecomastia.

The androgen resistance syndromes, including complete and partial testicular feminization (e.g. Reifenstein’s syndrome) are characterized by gynecomastia and varying degrees of pseudohermaphroditism. Kennedy Syndrome, a neurodegenerative disease, is also associated with decreased effective testosterone due to a defective androgen receptor (38). The gynecomastia is the combined result of decreased androgen responsiveness at the breast level and increased estrogen levels as a result of elevated androgen precursors of estradiol and estrone. As such, androgens in these diseases are not recognized by the peripheral tissues including the breast and pituitary. Androgen resistance at the pituitary results in elevated serum LH levels and increased circulating testosterone. The increased serum testosterone is then aromatized peripherally, promoting gynecomastia. Thus, gynecomastia is the result of increased estradiol levels which arise due to unopposed androgen unresponsiveness.


Other disease states have also resulted in gynecomastia.

Men with end stage renal disease may have reduced testosterone, and elevated gonadotropins. This apparent primary testicular failure may then lead to increased breast development (16).

The gynecomastia of liver disease, particularly cirrhosis, does not have a clear etiology. Some have speculated that the gynecomastia is the result of estrogen overproduction, possibly secondary to increased extraglandular aromatization of androstenedione, which may have decreased hepatic clearance in cirrhotics. However, testosterone administration to cirrhotics causes a rise in estradiol, but decreases the prevalence of gynecomastia (11, 3, 33). Therefore, although the association of gynecomastia with liver disease is apparent, current data are conflicting and the mechanism by which this occurs remains unclear.

As previously stated, thyrotoxicosis is associated with gynecomastia. Patients often have elevated estrogen which may result from a stimulatory effect of thyroid hormone on peripheral aromatase. Testosterone may also be increased possibly due to thyroid-hormone-stimulated increase in SHBG, as free testosterone is usually normal. Since SHBG binds testosterone more avidly than estradiol, there is a higher ratio of free estradiol to free testosterone. Thus, with normal testosterone and increased estrogen, there is an elevated estrogen to testosterone ratio. In addition, LH is also increased, which may also stimulate testicular estrogen synthesis (16, 9). gynecomastia can also follow spinal cord disorders. Most patients with spinal cord disorders display depressed testosterone levels and, in fact, can develop testicular atrophy with resultant hypogonadism and infertility. Some have speculated that this may result from recurrent urinary tract infections, increased scrotal temperature, and a neuropathic bladder, which ultimately cause acquired primary testicular failure. The exact mechanism, however, remains elusive (17).

Refeeding gynecomastia refers to breast development in men recovering from a malnourished state (13). Although most cases regress within seven months, the etiology of this phenomenon has not been fully elucidated.

HIV patients can also develop gynecomastia. There is a high incidence of androgen deficiency due to multifactorial causes, including primary and secondary hypogonadism (27).


A significant percentage of gynecomastia is caused by medications or exogenous chemicals that result in increased estrogen effect. This may occur by several mechanisms: 1) they possess intrinsic estrogen-like properties, 2) they increase endogenous estrogen production, or 3) they supply an excess of an estrogen precursor (e.g. testosterone or androstenedione) which can be aromatized to estrogen. Examples of drugs that cause gynecomastia are listed in Tables 2 and 3. Contact with estrogen vaginal creams, for instance, can elevate circulating estrogen levels. These may or may not be detected by standard estrogenic qualitative assays. An estrogen-containing embalming cream has been reported to cause gynecomastia in morticians (4, 12). Recreational use of marijuana, a phytoestrogen, has also been associated with gynecomastia. It has been suggested that digitalis causes gynecomastia due to its ability to bind to estrogen receptors (16, 35). The appearance of gynecomastia has been described in body builders and athletes after the administration of aromatizable androgens. The gynecomastia was presumably caused by an excess of circulating estrogens due to the conversion of androgens to estrogen by peripheral aromatase enzymes (8).

Drugs and chemicals that cause decreased testosterone levels either by causing direct testicular damage, by blocking testosterone synthesis, or by blocking androgen action can produce gynecomastia. For instance, chemotherapeutic drugs, such as alkylating agents, cause Leydig cell and germ cell damage, resulting in primary hypogonadism. Flutamide, an anti-androgen used as treatment for prostate cancer, blocks androgen action in peripheral tissues, while cimetidine blocks androgen receptors. Ketoconazole, on the other hand, can inhibit steroidogenic enzymes required for testosterone synthesis. Spironolactone causes gynecomastia by several mechanisms. Like ketoconazole, it can block androgen production by inhibiting enzymes in the testosterone synthetic pathway (i.e. 17a hydroxylase and 17-20-desmolase), but it can also block receptor-binding of testosterone and dihydrotestosterone (40). In addition to decreasing testosterone levels and biologic effects, spironolactone also displaces estradiol from SHBG, increasing free estrogen levels. Ethanol increases the estrogen to androgen ratio and induces gynecomastia by multiple mechanisms as well. Firstly, it is associated with increased SHBG, which decreases free testosterone levels. Secondly, it increases hepatic clearance of testosterone, and thirdly, it has a direct toxic effect on the testes themselves (27). Unfortunately, besides the drugs stated, a multitude of others cause gynecomastia by unknown mechanisms (Table 3).

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Table 3. Drugs that cause gynecomastia by uncertain mechanisms:
Cardiac and antihypertensive medications:
Calcium channel blockers (verapamil, nifedipine, diltiazem)
ACE Inhibitors (captopril, enalapril
b blockers

Psychoactive drugs:
Tricyclic antidepressants
Drugs for infectious diseases:

Drugs of Abuse:



Male breast cancer is rare and comprises only 0.2 percent of all male cancers. Although uncommon, it has been associated with gynecomastia and necessitates inclusion in the differential diagnosis. Other risks include Klinefelter’s syndrome, exogenous estrogen exposure, family history, and testicular disorders. It is unclear if these are specific risks for breast cancer are linked to the stimulatory process responsible for gynecomastia. New evidence suggests obesity and consumption of red meat may also raise the risk for the development of male breast cancer (19).



At presentation, all patients require a thorough history and physical exam. Particular attention should be given to medications, drug and alcohol abuse, as well as other chemical exposures. Symptoms of underlying systemic illness, such as hyperthyroidism, liver disease, or renal failure should be sought. Furthermore, the clinician must recall neoplasm as a possible etiology and should establish the duration and timing of breast development. Obviously, rapid breast growth that has occurred recently is more concerning than chronic gynecomastia. Additionally, the clinician should inquire about fertility, erectile dysfunction and libido to rule out hypogonadism, either primary or secondary, as a potential cause.

In our experience, the breast examination is best performed with the patient supine and with the examiner palpating from the periphery to the areola. The glandular mass should be measured in diameter. gynecomastia is diagnosed by finding subareolar breast tissue of 2 cm in diameter or greater. Malignancy is suspected if an immobile firm mass is found on physical examination. Skin dimpling, nipple retraction or discharge, and axillary lymphadenopathy further support malignancy as a possible diagnosis.

A thorough testicular exam is essential. Bilaterally small testes imply testicular failure, while asymmetric testes or a testicular mass suggest the possibility of neoplasm. Visual field impairment may suggest pituitary disease. Physical findings of underlying systemic conditions such as thyrotoxicosis, HIV disease, liver, or kidney failure should also be assessed.


All patients who present with gynecomastia should have serum testosterone, estradiol, LH and b HCG measured. Further testing should be tailored according to the history, physical examination and the results of these initial tests. An elevated b HCG or a markedly elevated serum estradiol suggests neoplasm and a testicular ultrasound is warranted to identify a testicular tumor, keeping in mind, however, that other non-testicular tumors can also secrete b HCG. A low testosterone level, with an elevated LH and normal to high estrogen level indicates primary hypogonadism. If the history suggests Klinefelter’s Syndrome, then a karyotype should be performed for definitive diagnosis. Low testosterone, low LH and normal estradiol levels imply secondary hypogonadism, and hypothalamic or pituitary causes should be sought. If testosterone, LH and estradiol levels are all elevated, then the diagnosis of androgen resistance should be entertained. Liver, kidney and thyroid function should be assessed if the physical examination suggests liver failure, kidney failure, or hyperthyroidism, respectively. Furthermore, if examination of breast tissue suggests malignancy, a biopsy should be performed. This is of particular importance in patients with Klinefelter’s syndrome, who have an increased risk of breast cancer.


Treatment of the underlying endocrinologic or systemic disease that has caused gynecomastia is mandatory. Testicular tumors, such as Leydig cell, Sertoli cell or granulosa cell tumors should be surgically removed. In addition to surgery, germ cell tumors are further managed with chemotherapy involving cisplatin, bleomycin and either vinblastine or etoposide (34, 14). Should underlying thyrotoxicosis, renal or hepatic failure be discovered, appropriate therapy should be initiated. Medications that cause gynecomastia should also be discontinued whenever possible based on their role in management of the underlying condition. Of course, if a breast biopsy indicates malignancy, then mastectomy should be performed.

If no pathologic abnormality is detected, then appropriate treatment is close observation. A careful breast exam should be done initially every 3 months until the gynecomastia regresses or stabilizes, after which a breast exam can be performed yearly. It is important to remember that some cases of gynecomastia, especially that which occurs in pubertal boys, can resolve spontaneously.


If the gynecomastia is severe, does not resolve, and does not have a treatable underlying cause, some medical therapies may be attempted. These include testosterone, dihydrotestosterone, danazol, clomiphene citrate, tamoxifen and the aromatase inhibitor testolactone. Testosterone treatment of hypogonadal men with gynecomastia often fails to produce breast regression once gynecomastia is established. Unfortunately, testosterone treatment may actually produce the side effect of gynecomastia by being aromatized to estradiol. Thus, although testosterone is used to treat hypogonadism, its use to specifically counteract gynecomastia is limited (42). Dihydrotestosterone, a non-aromatizable androgen, has been used in patients with prolonged pubertal gynecomastia with good response rates (22). Since dihydrotestosterone is given either intramuscularly or percutaneously, this may restrict its usefulness. Danazol, a weak androgen that inhibits gonadotropin secretion, resulting in decreased serum testosterone levels, has been studied in a prospective placebo-controlled trial, whereby gynecomastia resolved in 23 percent of the patients, as opposed to 12 percent of the patients on placebo (20). Unfortunately, undesirable side effects including edema, acne, and cramps have limited its use (27). Investigators have reported a 64 percent response rate with 100 mg/day of clomiphene citrate, a weak estrogen and moderate antiestrogen (24). Lower doses of clomiphene have shown varied results, indicating that higher doses may need to be administered, if clomiphene is to be attempted. tamoxifen, also an antiestrogen, has been studied in 2 randomized, double-blind studies in which a statistically significant regression in breast size was achieved, although complete regression was not documented (1). One study compared tamoxifen with danazol in the treatment of gynecomastia. Although patients taking tamoxifen had a greater response with complete resolution in 78 percent of patients treated with tamoxifen, as compared to only a 40 percent response in the danazol-treated group, the relapse rate was higher for the tamoxifen group (41). Although complete breast regression may not be achieved and a chance of recurrence exists with therapy, tamoxifen, due to relatively lower side effect profile, may be a more reasonable choice when compared to the other therapies. If used, tamoxifen should be given at a dose of 10 mg twice a day for at least 3 months (27). An aromatase inhibitor, testolactone, has also been studied in an uncontrolled trial with promising effects (45). Further studies must be performed on this drug before any recommendations can be established on its usefulness in the treatment of gynecomastia.


When medical therapy is ineffective, particularly in cases of longstanding gynecomastia, or when the gynecomastia interferes with the patient’s activities of daily living, then surgical therapy is appropriate. This includes removal of glandular tissue coupled with liposuction, if needed. In our experience, uses of delicate cosmetic surgical techniques are warranted to prevent unsightly scarring.


In summary, gynecomastia is a relatively common disorder. The causes of its development range vastly from benign physiologic processes to rare neoplasms. Thus, in order to properly diagnose the etiology of the gynecomastia, the clinician must understand the hormonal factors involved in breast development. Parallel to female breast development, estrogen, along with GH and IGF-1 is required for breast growth in males. Since a balance exists between estrogen and androgens in males, any disease state or medication that can increase circulating estrogen or decrease circulating androgen, causing an elevation in the estrogen to androgen ratio, can induce gynecomastia. Due to the diversity of possibly etiologies, including neoplasm, performing a careful history and physical is imperative. Once gynecomastia has been diagnosed, treatment of the underlying cause is warranted. If no underlying cause is discovered, then close observation is appropriate. If the gynecomastia is severe, however, medical therapy can be attempted and if ineffective, glandular tissue can be removed surgically.


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