Normal Estrogen Levels
Estrogen: To Kill or Leave?
This sub-topic was touched on briefly in the introduction, but too often in the bodybuilding and athletic community, aspects of nutrition, training, supplementation, and drug use with anabolic steroids succumb to extremism on both ends of the spectrum.
This is actually a trait we see in society at large, and in this case it has to do with estrogen.
While estrogen is indeed associated with anabolic steroid use, there are those who promote and advocate for the complete reduction and elimination of estrogen levels in the body while using anabolic steroids (and even while not using them), and then there are those who are on the extreme opposite end of the spectrum, advocating for allowing estrogen levels to skyrocket during anabolic steroid use without concern.
The human body is always actively working to maintain homeostasis.
Applied to biology and physiology, homeostasis is a system of regulating variables to keep internal conditions stable within the limits of the organism.
When an individual decides to participate in an anabolic steroid cycle, the body will attempt to maintain homeostasis and reduce its own endogenous androgen production in light of the large amounts of exogenous androgens entering the system by blocking or drastically reducing the activity of the hypothalamic-pituitary-testicular axis (HPTA)[1].
However, this is not the only attempt to maintain endocrine homeostasis.
This is because exogenously administered aromatized androgens interact with the aromatase enzyme to increase plasma levels of estrogen.
This is the body's attempt to lower excess circulating androgen levels and maintain hormonal balance.
Positive effects of estrogen
Estrogen, like cortisol, is too often mislabeled as a "bad" hormone.
While very high amounts of estrogen can have a number of undesirable effects on the body, it also plays a very beneficial role in many areas of the body:
- Cholesterol levels and cardiovascular function: There is a significant amount of evidence supporting the beneficial properties of estrogen on the cardiovascular system.
Premenopausal women are known to have a lower risk of cardiovascular disease than men and postmenopausal women [2], and studies have observed that normal physiologic levels of E2 (estradiol) in men can provide the same amount of cardiovascular protection as in women [3].
There is also evidence to support the therapeutic use of estrogen in cardiovascular physiology, as evidenced by improved cardiovascular function in male-to-female transsexuals and increased arterial reactivity (the elasticity of arteries) in men treated with high-dose estrogen [4].
In addition, a decrease in estrogen has been shown to have a detrimental effect on cholesterol levels, especially during anabolic steroid administration.
In one study, 280 mg of testosterone enanthate per week for 12 weeks resulted in a slight drop in cholesterol levels in subjects, as expected, but when an aromatase inhibitor was later administered, the cholesterol profile was worse, with a significant decrease in HDL cholesterol of 25% [5].
Estrogen is paramount to the proper functioning of the cardiovascular system, something that is already under pressure during an anabolic steroid cycle.
- Muscle growth, growth hormone, and IGF-1: Estrogen is believed to be involved in the proper function and regulation of human growth hormone (HGH) and insulin-like growth factor 1 (IGF-1), which are known to be very potent anabolic peptides in muscle tissue that are synthesized and secreted by the liver.
Specifically, HGH and IGF-1 have a number of anabolic effects.
These include the promotion of nitrogen retention and protein synthesis, as well as cell proliferation (myonuclear proliferation).
As shown in a study[6] that examined the effects of the anti-estrogen Nolvadex (tamoxifen) on these functions, decreased E levels lead to decreased circulating IGF-1, which negatively impacts overall anabolism.
Further research into the suppression of IGF-1 through the anti-estrogenic effects of Nolvadex showed that this suppressive effect on IGF-1 persisted even in the presence of the anabolic steroid testosterone [7].
This study not only examined the IGF-1 suppressive effects of Nolvadex in the presence of testosterone, but also the effects of testosterone without Nolvadex on IGF-1.
The results showed that IGF-1 levels increased when testosterone was administered alone, while Nolvadex significantly decreased IGF-1 levels with or without testosterone.
There is also evidence that estrogen has a positive effect on androgen receptors in that it increases the number of androgen receptors in muscle tissue and slows down the rate of androgen receptor degradation [8].
All of this information clearly points to the conclusion that normal circulating plasma levels of estrogen are very necessary for the normal functioning of muscle growth.
- Sexual function, libido, and fertility: The effects of estrogen on an organism's sexual function and fertility, both when it is deficient as well as when it is abundant, are remarkable.
Normal plasma estrogen levels are essential for the proper functioning of sexual desire and fertility, and a decrease in estrogen below the normal range can have significant negative effects on these areas of physiological function.
A man's sex drive is dependent on several factors, including
Estrogen and testosterone, as well as other molecules such as neurotransmitters.
One important study showed that both testosterone and estrogen are equally important in maintaining sexual function, and that subjects who were given an aromatase inhibitor to stop aromatization had a significant decrease in libido and sex drive [9].
This is also the effect of low estrogen levels, which many anabolic steroid users can anecdotally attest to from using high doses of aromatase inhibitors such as Letrozole (Femara), Arimidex (Anastrozole), and Aromasin (Exemestane).
Other studies have also demonstrated that estrogen plays an important role in regulating certain stages of sperm maturation and development in the gonads, and that disruption of estrogen levels results in temporary infertility until normal estrogen levels are restored [10].
Normal physiologic plasma estrogen levels, along with healthy levels of androgens, are highly necessary for proper sexual functioning in men.
- Preventing lethargy: It was mentioned in the introduction that the aromatase enzyme has been found to be present in significant concentrations in the central nervous system.
Many athletes and bodybuilders who use anabolic steroids have complained of a tremendous amount of lethargy when using strong aromatase inhibitors to significantly reduce the circulating levels of estrogen in the body during an anabolic steroid cycle.
This is commonly referred to as "steroid fatigue" or "estrogenic lethargy".
Returning to the activity of estrogen in the central nervous system, it is a confirmed fact that estrogen plays an important role in the regulation of the central nervous system, specifically the neurotransmitter serotonin, which is critical for maintaining a healthy and normal sleep/wake cycle and wakefulness [11] [12].
Disorders of the neurotransmitter serotonin have been proven to be associated with chronic fatigue in organisms [13] [14]. In this regard, decreased estrogen (E2) in postmenopausal women has been shown to result in chronic fatigue [15], and the same chronic fatigue has been clinically demonstrated in various patients using various aromatase inhibitors [16] [17] [18] [19], as well as anecdotally in anabolic steroid users who have used the same drugs for off-label purposes during steroid use to combat potential estrogenic side effects.
Maintaining a normal physiologic range of estrogen while using anabolic steroids is critical to maintaining a normal state of arousal.
When and how much to lower estrogen levels?
At this point, many readers are wondering: when should you start lowering your estrogen levels and for how long? The answer is not quite that simple, but it's not that complicated either.
First of all, if possible, you should always have a blood test done by a doctor whenever you are on an anabolic steroid cycle or using an aromatase inhibitor.
This will provide the most accurate picture possible of the anabolic steroid user's condition, and the definitive numbers provided by a blood test should be used.
It is impossible for an individual to 'feel' what level of estradiol (E2) is in their bloodstream.
Estradiol (E2) is the primary estrogenic product of aromatization, and is the level of concern for anabolic steroid users and men in general, and the normal and healthy levels of estradiol in plasma set by the medical community are between 14 and 55 pg/mL.
The units of measurement can vary depending on the units used in different countries, but picograms per milliliter (pg/mL) is usually the standard.
If a blood test is not available, the only way to know an individual's estrogen levels is through signs and symptoms, which are discussed in the next section of this article, Estrogen Side Effects.
Finally, if an aromatase inhibitor is used to lower estrogen levels, estrogen levels should not reach severely low levels for more than the minimum period of time (or more than a week) necessary to alleviate estrogen side effects.
Chronically low serum estrogen levels can lead to a number of disturbances in normal physiologic function, many of which can be extremely uncomfortable for the individual or pose significant health risks.
Many competitive and professional bodybuilders use strong aromatase inhibitors prior to competitions, but it is important to understand that these do not last more than a few days and are often very uncomfortable for the bodybuilder.
Medical references:
[1] Combination therapy of cyproterone acetate and testosterone enanthate as a potentially highly effective male contraceptive. C Meriggola et al. J Clin Endocrinol Metab 81(8) 3018-23, 1996.
[2] Rosano GM, Panina G (1999). "Estrogen and the heart". Therapeutics 54(3): 381-5. PMID 10500455.
[3] Alliomaki K et al. 1996. Clinical features of primary ovarian failure due to point mutations in the follicle stimulating hormone receptor gene. J Clin Endocrinol Metab. 81:3722-6.
[4] Espey LL and H Lipner. 1994. ovulation. In: E. Knobil and J Neill, eds. Physiology of reproduction, 2nd edn . New York: Raven Press, pp. 725-80.
[5] High-density lipoprotein cholesterol is not reduced by administration of aromatized androgens. Friedl K, Hannan C, et al. Metabolism 39(1) 1990.
[6] Effects of tamoxifen, aminoglutethimide, and goserelin on human plasma IGF-1 levels in breast cancer patients. J Steroid Biochem Mol Bio 41:5413, 1992.
[7] Activation of the somatotropic axis by testosterone in adult males: evidence for the role of aromatization. Jacqueline. Endocrinol Metab 76:1407-12 1993.
[8] Regulation of cytoplasmic androgen receptors in rhabdomyolysis by sex steroids. Endocrinology. September 1984. 115(3):862-6.
[9] Malnick S, Somin M, Goland S. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013 Dec 19;369(25):2456. doi: 10.1056/NEJMc1313169#SA4.
[10] Breedlove, SM, and AP Arnold. 1980. Hormone accumulation in the sexually dimorphic motor nucleus of the rat spinal cord. Science 210:564-6.
[11] Zenab Amin et al. Effects of estrogen-serotonin interactions on mood and cognition. Behav Cogn Neurosci Reviews 4(1) 2005:43-58.
[12] Chiara M Portas et al. Serotonin and the sleep/wake cycle: special emphasis on studies of otodialysis. Progress in neurology 60(200) 13-35.
[13] Reduced serotonin transporter in patients with chronic fatigue syndrome. Neuroreport 2004 Dec 3;15(17):2571-4.
[14] Narita M et al. Association between serotonin transporter gene polymorphisms and chronic fatigue syndrome. Biochem Biophys Res Commun 2003 Nov 14;311 (2)264-6.
[15] Dickerson LM et al. Premenstrual syndrome. Am Fam Physician 2003 Apr 15;67(8):1743-52.
[16] The "Stages of Anastrozole in Women with Asymptomatic Mullerian Cancer" Trial. Obstetrics & Gynecology On Call. December 2003;91(3):596-602.
[17] Letrozole. A review of its use in postmenopausal women with advanced breast cancer. Pharmaceutics. December 1998;56(6):1125-40. review.
[18] Exemestane: a review of clinical efficacy and safety. Breast. June 2001;10(3):198-208.
[19] A study of a new aromatase inhibitor, fadrozole, in postmenopausal women with advanced metastatic breast cancer. J Clin Oncol. 1992 Jan;10(l):111-6.
