Why is hCG on WADA’s list?

Annually, the list of substances on the World Anti-Doping Agency’s list of prohibited substances is revisited, revised and made public. On this list includes substances prohibited during competition and even out of competition, banned designer drugs, and drugs still in pre-clinical trial, and veterinary drugs. As you can imagine, this means the list is very comprehensive as athletes have been known to take advantage of information not in ‘black and white.’

How does WADA determine if a drug should be on the list?

For a drug, an alternative sports recovery method and any substance to be added to the list, it must enhance sports performance, violate the fairness, standards of morality and cleanliness of the modern sports spirit and affect the health of the athlete in some way.

This is because apart from the underlying reason of fairness and unity in sports WADA tries to promote, the athlete might argue-- and with good reason too, that at the end of the day, the choice is theirs. But WADA, sports promoters and the sports bodies of every country has a duty and responsibility to protect her athletes to the best of their ability.

In their bid to ensure they remain a step ahead of dopers and questionable laboratories who sponsor dopers, the WADA list is so comprehensive many substances find their way into the list.

One of these is human Chorionic Gonadotropin. (hCG)

What is hCG?

Human chorionic gonadotropin is a glycoprotein secreted by the syncytial trophoblast cells in the human placenta. Usually, if fertilization does not occur, the corpus luteum stops secreting progesterone and eventually dies out.

The secretion of the hCG causes the maintenance of the corpus luteum. Therefore, it continues to secrete progesterone and the pregnancy is maintained. Human chorionic gonadotropin can be detected 8-9 days after ovulation. As a result, its presence is used in detecting pregnancy. Human chorionic gonadotropin is a vital hormone of pregnancy.

Then why is it on WADA’s list of banned substances?
A look at the chemistry and physiology of its action sheds more light on the answer to this question.

Chemistry of action

Human chorionic gonadotropin is a 39000 molecular weight glycoprotein. The major chemical effect of human chorionic gonadotropin that makes it a player in the world of performance-enhancing drugs is its similarity in structure and function to the luteinizing hormone produced by the pituitary gland.

_{By Borislav Mitev - borislav_mitev@hotmail.com (PyMOL) Public domain via Wikimedia Commons, CC BY-SA 3.0}

Luteinizing hormone is produced by the anterior pituitary gland in both males and females. The luteinizing hormone regulates the action of the ovaries and the testes. It also controls their secretory activities.

Like the human gonadotropin hormone, the luteinizing hormone is also a glycoprotein with an alpha and beta subunit.

Physiology of action (Male)

As a natural hormone of pregnancy, hCG is produced at undetectable to very low levels in men. A significant level of hCG in men might be indicative of the presence of an underlying pathophysiology.

Due to its similarity in structure and function to luteinizing hormone, hCG can be used medically to manage conditions stemming from a lack of luteinizing hormone and testosterone. Luteinizing hormone regulates testosterone production by controlling its secretion by the Leydig cells. hCG can be used as a luteinizing hormone replacement in abnormalities of testosterone production.

Physiology of action (Female)

The human chorionic gonadotropin causes the proliferation of the corpus luteum and the maintenance of pregnancy. As a result, the corpus luteum continues its secretion of progesterone in the first three months of pregnancy.

hCG could also play a vital role in the development of the immune system.
Its similarity in function and structure to the anterior pituitary luteinizing hormone expands its range of function to include times when luteinizing hormone would be needed. So it can be used to induce ovulation and in fertility treatment.

Effect on female performance

Due to its role in pregnancy, human chorionic gonadotropin has no observable effect in boosting female athletic performance.
For this reason, the hCG being on the banned list is mostly for the benefit of the male athlete.

Effect on male performance

On May 2010, baseball player, Manny Ramirez tested positive for hCG. He is not the first male athlete to test positive for the hormone.

What benefit would hCG confer on the male athlete?

Due to its similarity in structure and function to luteinizing hormone, hCG can be used by androgen dopers to hide the effect of their physiological actions. In this way, it can be used as a masking agent. hCG can also help increase protein synthesis and improve muscular strength by mimicking the action of the luteinizing hormone in the male.

When an athlete uses synthetic androgenic drugs, it stimulates a negative feedback loop through the hypothalamic pituitary-gonadal-axis that shuts down the natural production of the androgen steroid.
This ‘shutting down’ is beneficial to the human physiology because if the natural steroid is produced and circulates along with the synthetic one, it would lead to an overstimulation of every organ involved.

Yet, the circulation of the synthetic androgens and the suppression of the body’s natural secretion is what gives the athlete away and alerts the sports regulatory body of his guilt. hCG acts as a masking agent by helping to bring balance to the circulatory levels of testosterone and helps the athlete escape detection.

Usually, the presence of synthetic androgens causes the hypothalamus to suppress production of gonadotropin-releasing hormone (GnRH) which would have stimulated the anterior pituitary to release luteinizing hormone. The luteinizing hormone would then travel to the testis to stimulate testosterone production.

Overuse of synthetic androgens and the over suppression that would follow might lead to testicular atrophy. By mimicking the action of Luteinizing hormone, hCG ‘reminds’ the body to continue producing testosterone and thus restores testicular function.

Negative effect of hCG

• Gynecomastia (growth of breasts in men)

_{By JMZ1122 Dr. Mordcai Blau www.gynecomastia-md.com CC BY-SA 3.0], from Wikimedia Commons}

• Acne
• Headaches
• Depression
• Bloating
• Mood swings
• Impaired testicular function

In conclusion, for a lesser known 'androgenic' drug compared to the traditional synthetic androgens, hCG is actually in a class of its on. It combines a dual purpose-- as an androgen ‘masking agent’ with a luteinizing hormone mimic to bring an overall balance to a cheating performance. The athlete might escape testing positive for synthetic androgen because hCG will bring balance and the danger of impaired testicular function due to synthetic androgen abuse might also be avoided due to the action of hCG.

Yet, the athlete has no escape.

This is because the circulating hCG comes with its own slew of problems. One of which is gynecomastia, an increase in the size of the male breasts. To combat this effect, some athletes also take an estrogen blocker and another masking agent to hide the effect of the estrogen blocker.

Just like borrowing from Peter to pay Paul. But at the end of the day, Paul is still being owed.

References

Prohibited list
Why do athletes use hCG?
Human chorionic gonadotropin
Luteinizing hormone
What is the normal hCG level in men?
Performance and image enhancing drugs
Guyton, Arthur C, and John Hall, Textbook of Medical Physiology. Elsevier, 2000.