Hormonal Health: Optimizing Estrogen in Men and Women

Hormonal Health: Optimizing Estrogen in Men and Women

ATP LAB

By Dr. Dwayne N. Jackson, PhD


In terms of female endocrinology, no other hormone receives as much attention as estrogen; after all, it is one of two major female sex hormones (the other is progesterone). But, men also require optimal estrogen levels for health and survival, however in much lower amounts than females.


In females, the ovaries are the main producers of endogenous estrogens, but estrogens are also generated in adipose (fat) tissue and in the adrenal glands of the kidney. For males, the adrenals and adipose tissue are main sources of estrogen.


As you likely already know, testosterone is the primary sex hormone in males, but healthy females also produce only small amounts of this androgen.


Why is estrogen ‘balance’ so important?

Believe it or not, in male and females, the main starting materials for estrogen production are androgens (testosterone and adrostenedione). Through modification via aromatase enzymes (more on this later), androgens are converted to estrogen, which is an essential healthy step for glucose control, cardiovascular health, immunity, bone health, fertility, sexual health, and neural function in males and females.


Although healthy levels of endogenous estrogen provide health protection, deviations in the body’s estrogen levels (above or below normal) lead to many human pathologies. That is, both hypo and hyper levels of estrogen have been linked to chronic and acute diseases in humans. Healthy aging is associated with estrogen imbalance, a condition that leads to the loss of bone and muscle tissue, glucose intolerance, insulin insensitivity, and accumulation of body fat. Beyond such changes in musculoskeletal and metabolic health, increasing cases of polycystic ovary syndrome, infertility, breast cancer, ovarian cancer, and gynecomastia (female breast development in males) indicate that ‘estrogen dominance’ is becoming a serious problem in men and women worldwide.


FROM: Biomed Pharmacother. 2018 Jun;102:403-411.


Estrogen Dominance: Why is this happening?

Like most hormones, estrogen acts through its specific estrogen receptors, estrogen-receptor-alpha (ER) and estrogen-receptor-beta (ER). When we discuss estrogen dominance, we are talking about the heightened influence of estrogen relative to that of androgens. So, estrogen dominance relates to increases in the amount of circulating estrogen available to activate estrogen receptors, and/or an increase in the number of receptors available for interactions with estrogen--- all at the cost of decreased androgenic influences.


So, as you can see, when discussing the good and bad of estrogen, it’s much more complicated than simply discussing it as “too high” or too low”.  In fact, what ultimately determines estrogen’s impact on our health and performance comes down understanding how we accumulate exogenous estrogens (from the environment), how we produce estrogen and metabolize endogenous estrogen (in the body), and the level of ER and ER expression in the target tissues. The following list outlines the key factors and reasons how estrogen dominance has become a global concern:

  • Increasing exposure to environmental contaminants and drugs:

Estrogen levels increased by:

  • Habitual use of alcohol, marijuana, heroin, cannabis, methadone, amphetamines
  • Bisphenol A (BPA) and phthalates used in plastics
  • Prescription antidepressants
  • Cosmetic fragrances

Estrogen levels decreased by:

  • Prescription antidepressants, antipsychotics, anticonvulsants, opiates, estrogens, anti-androgens, anti-hypertensive drugs, and H2-receptor antagonists.
  • Drugs that increase prolactin levels in the body (those mentioned above)

Aging Population:
  • In females, estrogen levels decrease as menopause approaches. This fall in estrogen signals for increased expression of estrogen receptors in tissues throughout the body. This makes the body more sensitive to estrogen exposure and is one of the mechanisms driving ER-positive breast cancer.
  • In males, estrogen levels increase with aging, as activity level generally decreases, testosterone levels decrease, muscle mass tends to decrease, and body fat goes up. This cascade of aging events promotes overexpression of aromatase and further processing of testosterone to estrogen, creating a ‘snowball effect’ of high estrogen and low testosterone in aging males.    

Elevated Body Fat:

Obesity is an epidemic in North America and it’s no coincidence that the fatter we get, the greater the prevalence of disease caused by hormonal disturbances. In fact, most of the hormonal-related health issues discussed in this article can be circumvented by achieving a healthy body fat level.


  • Increased body fat promotes the production of inflammatory cytokines that activate aromatase. Since androgens are metabolized to estrogens, this sets up a condition of high estrogen and low testosterone in males and females.
  • Inflammation

Although high body fat levels promote robust inflammation, there are also a number of chronic inflammatory conditions which occur independent of body fat.


  • One of the most common drivers of chronic inflammation in athletic and lean populations is psychological stress. That’s right, your mental state can significantly drive inflammation and impact testosterone and estrogen homeostasis.
  • Autoimmune inflammatory disorders (e.g., rheumatoid arthritis) also promote aromatase activity to drive estrogen levels up and androgen levels down.

The data suggest that, regardless of sex, if we can control inflammation and aromatase activity, we can balance estrogen and optimize health and performance.


What is aromatase and how is estrogen produced and metabolized?


Estrogens come in many varieties. Estradiol is the form of estrogen primarily responsible for female development, and to some extent male development. However, when discussing the positive and negative properties of estrogen, we must consider estradiol’s metabolites. The first step in estradiol metabolism is exclusively oxidative and involves a subsequent series of hydroxylation steps.


P450 (CYP) enzymes, reside in abundance in the liver, but can also be found in high levels in skin and body fat. It is the regulation of these enzymes that ultimately determines the production and fate of estrogen and estrogen-like compounds in the body. It’s through these enzymes that our bodies produce “good estrogen” and “bad estrogen”.


Modifications to estradiol can be activated or deactivated by endogenous or exogenous compounds that influence the P450CYP enzymes that act on specific sites on the molecule. This modulation of estrogen, through hydroxylation, is essential since some of the metabolites can be harmful, while others are healthy. An example of a healthy estrogen metabolite is 2-hydroesterone, which is formed when the enzyme CYP1A1 interacts with estradiol. 2-hydroesterone is considered “healthy” as it has low estrogenic activity, despite high affinity for estrogen receptors—resulting in decreased estrogenic influences at the target tissue.


An example of harmful estrogen metabolites are 16--hydroxyesterone and 4-hydroxyestradiol. Of the CYP P450 enzymes, CYP1B1 has the highest levels of estrogen hydroxylation activity and expression levels in breast tissue. CYP1B1 metabolizes estradiol to form 4-hydroxyestradiol and 16--hydroxyesterone.  Both forms of estrogen have been implicated in the initiation of cancer. Research tells us that any endogenous or exogenous factor that increases in the activity of the CYP1B1 enzyme, resulting in increased 4-hydroxyestradiol and/or 16--hydroxyesterone, may also increase cancer risk.


Diet and Exercise Positively Impact Estrogen Metabolism


Dietary factors can determine the balance of estrogen metabolism. High protein and high omega 3 fatty acid diets increase healthy 2‐hydroxylation of estrogen, while high carbohydrate and high omega 6 fatty acid diets resulted in a decrease in healthy 2‐hydroxylation.


Research has shown that 2‐hydroxylation of estradiol is markedly depressed in overweight people. Conversely, heavy dieting and vigorous exercise have been shown to promote the production of this healthy estrogen. In fact, one of the main reasons why healthy women stop ovulating when they train or diet heavily is because they increase 2‐hydroxylation of estradiol so much that their overall estrogenic activity is too low.


A dietary supplemental approach to overcoming estrogen dominance


We now know that many of the foods we eat contain compounds that modify the expression and activity of many CYP P450 enzymes. In an attempt to naturally balance estrogens in males and females for optimal health and performance, there has been an enormous effort to isolate and increase the bioavailability of many of these compounds.


It’s through careful consideration of the data from the aforementioned studies that we formulated ATP LAB ESTRO CONTROL. Below, I have highlighted the 3 key ingredients that make our premium ESTRO CONTOL formulation the best estrogen balance supplement, for men and women, currently available.


BioResponse DIM®  (Diindolylmethane)


Each capsule of ATP Lab Estro Control contains 100 mg of patented Bioresponse DIM.


Diindolylmethane (DIM) is a chemical formed by your body when you eat cruciferous vegetables like broccoli, cauliflower, Brussels sprouts, and cabbage. These green veggies contain the phytochemical indole-3-carbinol (I3C), which the body converts into DIM. DIM works by optimizing the activity and regulation of CYP enzymes (described above) in a positive manner. One of DIM’s main effects is to increase the efficacy of CYP1A1, which promotes the metabolism of potent estrogens into their healthy and mildly estrogenic metabolite, 2-hydroesterone. Numerous studies have shown that DIM also shifts estradiol metabolic pathways away from unhealthy C‐16 and C‐4 hydroxylation by inhibition of CYP 3A4 and CYP 1B1. Inhibition of both of these pathways blunts the formation of two unhealthy and carcinogenic estrogen metabolites: 16‐hydroxyestrone and 4‐hydroxyestrone.


Why don’t most DIM supplements work?


Taken in supplement form, DIM by itself has zero bioavailability. BioResponse DIM is the only patented and microencapsulated form of DIM currently available. BioResponse DIM is also the first (and only) diindolylmethane ingredient with proven release for enhanced and predictable absorption. Other DIM supplements on the market have no meaningful absorption without microencapsulation, even at a 3 times greater dose. No studies have shown that black pepper (piperine or Bioperine) works as an additive to generic DIM to improve absorption. Our formulation contains pure DIM, not I3C, the unstable indole. According to the Bioresponse website, all published clinical trials examining DIM have only used BioResponse DIM, including clinical trials sponsored by the National Cancer Institute.


Acumin® Turmeric extract (Curcuma Longa) (Rhizome) 60 mg


Each capsule of ATP Lab’s Estro Control has a clinically relevant 60mg of Patented Acumin.


Curcumin is a compound that has antibacterial, antiviral, anti-inflammatory, and anticancer properties and has been used for centuries in Ayurveda, the ancient natural healing system of India. Recently, science has been able to unravel the medicinal potential of this ancient herb.


Acumin is a patented turmeric supplement that has superior bioavailability to other generic forms of turmeric. In fact, clinical research has shown that subjects who took patented Acumin (like that used in ATP Lab’s Estro Control) had 5-6x greater concentration of blood curcuminoids (the active ingredient in turmeric), compared to those who received standard forms of turmeric. Although the benefits of supplemental curcuminoids are broad and plenty, for the purposes of this article, we will focus on two primary reasons we have included Acumin in Estro Control.


First, adding Acumin enables us to attack estrogen dominance by decreasing the expression of estrogen receptors (specifically, ER), an effect that decreases systemic estrogenic influences. As well, curcuminoids are potent regulators of nuclear factor-KB (NF-kB). NF-kB is a pro-inflammatory genetic modifier which has been implicated as the link between estrogen and cancers under conditions of systemic inflammation. Research has shown that most of the health protection we get from curcumin is due to downregulation of NF-kB and its pathway intermediates. As discussed above, stress, high body fat, and environmental toxins all increase our inflammatory load. So, keeping the NF-kB pathway in check should be a priority for everyone.


BroccoPhaneTM 100 mg


Each capsule of ATP Lab’s Estro Control has a clinically relevant 100 mg of Patented BroccoPhane. Patented BroccoPhane® is broccoli sprout powder, which is standardized for sulforaphane—a potent antioxidant. Clinical studies suggest that sulforaphane’s antioxidant potential increases the activity of phase II detoxfication enzymes, which serve to modify estrogens into their healthy forms. Remarkably, some data also show that sulforaphane supports healthy phase I enzymatic hydrolysis of estrogens (like DIM, see above). The phase II detoxification pathway provides a ‘last chance’ for excess estrogens to be removed from the circulation. Before the invention of BroccoPhane, supplement formulators struggled to find compounds that efficaciously activate this essential detoxification pathway. 


So, how does patented BroccoPhane work?


Phase II detoxification enzymes play an important role in biotransformation of estrogen. The majority of these enzymes are transferases and include UDP-glucuronosyltransferases, sulfotransferases, glutathione S-transferases, N-acetyltransferase, and S- and O-methyltransferases.


In addition to direct activation of PII detoxification enzymes, sulforaphane activates the KEAP1/NRF2 pathway (the body’s major regulator of cellular protection in response to oxidative stress), which promotes an increase in several of the phase II detoxification enzymes mentioned directly above. At the end of the day, many of these enzymes are intimately involved in reduction of oxidative species through regulation of glutathione metabolism and quenching of free radicals. Glutathione works to decrease health burden of excess estrogens by forming conjugates with them, resulting in an increase in the more healthy and weaker forms of estrogen in the circulation.


How can you protect yourself from excessive inflammation and estrogen dominance?


We created Estro Control to attack estrogen dominance in males and females.


FEMALES: We suggest taking 1 capsule with breakfast for the first week (1 per day), then increase this dose to 1 capsule with breakfast and 1 capsule with dinner (2 per day).


MALES: We suggest taking 1 capsule with breakfast (1 capsule per day).


For best results, we recommend cycling Estro Control by taking it continuously for 2-3 months, with one month off between cycles.


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