In part I of this series we discussed the effects of anabolic-androgenic steroid (AAS) use on the heart, the blood, cholesterol, and the liver. We also suggested some treatment options for the physician or health care provider. In this final installment we will discuss the side effects of the endocrine system including the testis, as well as the thyroid, prostate, and cosmetic issues. We’ll also list some less commonly reported side effects.
AASs are synthetic versions of testosterone. As such, they interfere with the body’s endocrine system when present in supraphysiological amounts. The body’s endocrine system is regulated in large part through feedback inhibition. The system of interest to bodybuilders, and the one to show the greatest disruption, is the hypothalamic-gonadal-pituitary axis. This axis involves, gonadotrophin-releasing hormone (GnRH), leuteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (Test), and estrogen.
The adult testis has two important roles, namely the production of spermatozoa (fertility) and the secretion of testosterone which is needed for the expression of secondary sexual characteristics. These functions depend on stimulation by the pituitary gonadotrophins, FSH and LH, which are stimulated by hypothalamic GnRH. Testosterone is secreted by the Leydig cell in the testis under LH stimulation and is essential for promoting spermatogenesis. Testosterone secreted by the testis is then converted by aromatase into estrogen in target tissues.
Upon beginning AAS treatment, LH and FSH become undetectable within 2 weeks with as little as 250mg/week of testosterone cypionate. 100mg/week will cause complete shut down of LH and FSH within 5 weeks. This results in significantly lowered testosterone production and infertility.
Treatment options:No treatment options are recommended unless the individual is trying to conceive, or until the individual discontinues the use of AASs. Upon cessation of AASs use a reduction in estrogenic activity can be sufficient to restore normal hypothalamic-gonadal-pituitary axis activity. Clomid (Clomiphene citrate) is the most favorable drug to use, having anti-estrogen activity at both the hypothalamus and pituitary but not anti-androgen or anti-aromatase activity.
In cases where conception is important, hCG and menotropins can be used during or after AAS use. See “treatment options” under “Testicular” for more information.
Testicular atrophy is common with long term AAS use. When LH and FSH levels fall, the testis begin to shrink from disuse essentially. If this continues long enough, there will even be a loss of leydig cells through apoptosis. Leydig cells produce testosterone. Once this occurs, the capacity of the testis to produce testosterone is greatly reduced. This poses a significant problem once the individual decides to discontinue use of AASs. The atrophied testis are often unable to produce enough testosterone to maintain levels in the normal range. Testicular atrophy can also cause infertility. (1,2)
Treatment options: Pregnyl (hCG) is the recommended treatment to prevent testicular atrophy while using supraphysiological doses of AASs. Menotropins Intramuscular (hMG) is often useful as adjunct therapy to return the testis to full functionality and ensure fertility.
Testicular atrophy can be corrected while the individual is using AASs by intermittent hCG therapy. If using Pregnyl alone, 500 IUs 2-3 times per week should be used until the testis return to normal size as measured with a Prader orchidometer. Normal testicular size is defined as 15–25 ml. Having baseline values for testicular size for that patient is helpful. After normal testicular size is achieved, hCG can be used intermittently to maintain normal testicular volume.
Prior to menotropins/hCG therapy to stimulate spermatogenesis in males with primary or secondary hypogonadotropic hypogonadism, pretreatment with hCG alone is required. The usual pretreatment dosage of hCG is 500 USP units 3 times weekly until normal serum testosterone concentrations are achieved. Pretreatment with hCG may require 4–6 months if the individual has used AASs in high doses for several years. Once normal testosterone levels have been achieved, concomitant therapy with menotropins can be initiated. The usual initial dosage of menotropins to stimulate spermatogenesis is 75 IU of FSH and 75 IU of LH 3 times weekly in conjunction with hCG 500 USP units 2 times weekly.
Menotropins/hCG therapy should be continued for at least 4 months to ensure normal sperm count, since it takes approximately 70–80 days for germ cells to reach the spermatozoa stage. If evidence of increased spermatogenesis does not occur following 4 months of menotropins/hCG therapy, treatment can be continued at the same dosage, or dosage of menotropins may be increased to 150 IU of FSH and 150 IU of LH 3 times weekly; dosage of hCG should not be changed.
AASs can decrease serum T4-binding globulin (TBG) concentrations dramatically. Research has shown that chronic use of high dose AASs can lower T3 levels as well. (3,4) This is generally non pathologic and requires no immediate treatment, as levels usually remain in the lower normal range and should return to normal upon cessation of AAS use. The exact mechanism by which AAS interferes with thyroid function isn’t clear at this time.
In a study of the effect of exogenous testosterone (administered transdermally or parenterally) on serum prostate-specific antigen (PSA) concentrations in men with hypogonadism, no correlation between testosterone therapy and PSA or prostate-specific membrane antigen was demonstrated. (5) Later studies also were unable to show an influence of testosterone on the risk of developing prostate cancer in normal healthy males. (6,7) No clear relationship between testosterone replacement therapy and prostate cancer has been established to date, although anecdotal reports have been published; additional long-term studies are needed to clarify the potential risk.
Gynecomastia is the benign growth of glandular tissue of the male breast. Among AAS using individuals, it is caused by the peripheral aromatization of androgens into estrogens. The increase in circulating estrogens causes proliferation of breast tissue cells and subsequent enlargement of the breast mass.
It should be suggested to the patient exhibiting severe gynecomastia that replacing aromatizable androgens such as the testosterone esters with a non-aromatizable androgen will reduce this particular side effect. Care should be taken however to monitor cholesterol levels should a switch be made to non-aromatizable androgens as they are known to negatively effect cholesterol levels.
Non-surgical:Nearly all of the auxiliary drugs taken by AAS using individuals to combat side effects, will be anti-estrogenic compounds. It is important for the physician to be aware of any additional drugs a patient may be taking in order not to overdose the patient.
Drug management therapies for gynecomastia involve reducing estrogen activity by either blocking the estrogen receptor and/or inhibiting peripheral aromatization of androgens. Tamoxifen citrate (Nolvadex) and Clomiphene citrate (Clomid) are suggested for competitive inhibition of estrogenic activity at the estrogen receptors, while Anastrozole (Arimidex) is suggested for aromatase inhibition.
Surgical: The surgical treatment for gynecomastia has had variations since 1538, when the first description of the surgical treatment was attributed to Paulus Aegineta. Since then, various incisions on and under the breast have been used. It is suggested that when gynecomastia is severe, the excess skin should be removed along with the gland and fat. Surgical treatment usually results in permenant resolution of gynecomastia, however, if some breast tissue is unknowingly missed, symptoms can return if high dose AAS use continues.
Alopecia (Male pattern baldness)
AAS induce alopecia by shortening the anagen phase and increasing the number of hairs that are in the telogen phase. Men with androgenetic alopecia typically have a receding hairline and moderate to extensive loss of hair, especially on the front and top of the head. The remaining hair tends to feel a little finer and shorter than normal. AAS can induce alopecia in genetically susceptible individuals still in their teenage years.
Although there is no cure for androgenic alopecia in genetically susceptible individuals, it can be “managed” with minoxidil and/or finasteride. Minoxidil is an over-the-counter drug approved by the FDA for stimulating new hair growth and preventing further hair loss in cases of hereditary balding. Minoxidil is rubbed into the scalp twice a day. Oral finasteride (Propecia, Proscar) is an FDA-approved drug for baldness and the only one available in pill form (one pill/day). Finasteride blocks the formation of the hormone dihydrotestosterone (DHT), which is responsible for shrinking hair follicles and is believed to be a significant factor in hereditary baldness or thinning.
All AAS have at least some androgenic activity. As a result, acne is a common side effect of AAS use. High dose AAS increase skin surface lipids, the cutaneous population of Propionibacteria acnes and the cholesterol and free fatty acids of the skin surface lipids. Acne, oily hair and skin, sebaceous cysts, hirsutism, androgenic alopecia, striae atrophicae, seborrheic dermatitis, and secondary infections including furunculosis may occur depending on the dose of AAS and the individuals susceptibility to such side effects.
The goal of any strategy for acne treatment is to do one or more of the following: Reduce sebum production, reduce Propionibacteria acnes, and normalize the shedding of skin cells.
Mild acne can usually be managed with proper cleansing and maintenance of the skin along with over-the-counter medications such as benzoyl peroxide and/or salicylic acid preparations. If these measures are unsuccessful, the physician may prescribe other medications such as antibiotics, and/or retinoids.
Miscellaneous side effects associated with AAS
- Flushing of the skin
- Sleep apnea
- Loud snoring
- Priapism (chronic erection)
- Enlargement of the clitoris
- Altered libido
1. Turek PJ, Williams RH, Gilbaugh JH, Lipshultz LI 1995 The reversibility of anabolic steroid-induced azoospermia.J Urol153:1628–1630
2. Martikainen H, Alen M, Rahkila P, Vihko R 1986 Testicular responsiveness to human chorionic gonadotropin during transient hypogonadotropic hypogonadism induced by androgenic/anabolic steroids in power athletes.J Steroid Biochem25:109
3. Deyssig R., Weissel M. Ingestion of androgenic-anabolic steroids induces mild thyroidal impairment in male body builders.J Clin Endocrin Metab. 76(4): 1069-1071, 1993
4. Markku A., Rahkila P., Reinila M., & Vihko R. Androgenic-anabolic steroid effects on serum thyroid, pituitary and steroid hormones in athletes.Am J Sports Med. 15(4):357-361, 1987.
5.Endocr Pract.1996; 2:440-53.
6. Mohr BA, Feldman HA, Kalish LA, Longcope C, McKinlay JB. Are serum hormones associated with the risk of prostate cancer? Prospectiveresults from the Massachusetts Male Aging Study.Urology. 2001 May;57(5):930-5.
7. Dorgan JF, Albanes D, Virtamo J, Heinonen OP, Chandler DW, Galmarini M, McShane LM, Barrett MJ, Tangrea J, Taylor PR. Relationships of serum androgens and estrogens to prostate cancer risk: results from a prospective study in Finland.Cancer Epidemiol Biomarkers Prev. 1998 Dec;7(12):1069-74.