What are progesterone metabolites and how are they related to cancer?
In a new video, An Oasis of Healing senior medical staff member Dr. Nathan Goodyear addresses the topic of progesterone metabolites and cancer, as part of a weekly in-house staff education program. In these sessions, Dr. Goodyear leads the discussion on pertinent cancer-related topics and how it relates to An Oasis of Healing’s comprehensive care program and their patients’ healing journeys.
First off, let’s review. What is progesterone and what does it do?
Progesterone is a hormone secreted by a temporary endocrine gland produced by the female body after ovulation, during the second half of the menstrual cycle. It prepares the endometrium for the possibility of pregnancy after ovulation.
It triggers the lining to thicken, in preparation for a fertilized egg. When the body is producing high levels of progesterone, it will not ovulate.
If no fertilization occurs, the corpus luteum (the temporary endocrine gland) breaks down, thus lowering the body’s progesterone levels. This, then, triggers menstruation.
If the woman does become pregnant, the progesterone works to stimulate the body to provide blood vessels to the endometrium to nourish the growing fetus. The placenta also secretes progesterone once developed, and this is the reason why the body does not produce more eggs throughout the pregnancy.
According to Dr. Goodyear, there is a lot of correlation between estrogen and progesterone metabolites.
He explained, “Again when we talk about ER (estrogen receptor) positive breast cancer, or other types of cancers, we’re referencing ER-alpha. That’s a particular receptor for estrogen, but there’s also an ER beta, so when you look at estrogen there’s ER alpha and ER beta.
ER alpha promotes proliferation and inhibits apoptosis, so it promotes cancer. When you see somebody that has ER-alpha-positive breast cancer, that’s alpha. ER beta inhibits ER alpha, so it inhibits proliferation, it promotes apoptosis.”
Dr. Goodyear further noted that in breast, prostate, ovarian or colon cancer, the loss of ER beta is “paramount” to the stimulation and initiation of carcinogenesis or the formation of cancer.
ER beta inhibits ER alpha, so in turn, it inhibits proliferation and promotes apoptosis.
There are two pathways in progesterone metabolism. One is 5-alpha reductase, and another one is driven by 3-alpha and 20-alpha hydroxy steroid oxide reductase. 5-alpha reductase is the enzyme which converts testosterone into DHT (5-alpha-dihydrotestosterone)—a “potent androgen involved in male sexual differentiation.”
He added, “5 alpha-reductase promotes 5 alpha pragmeme, the others promote 4 alpha. Pro cancer and anti-cancer. These pathways really are showing us which way the person’s going.
When you look at 5 alpha hydroxy progestogen metabolite and 3 alpha, when given at the same time, inhibits 5 alpha hydroxyprogesterone. ER beta will regulate the metabolite of progesterone, 3 alpha, which is a 4 alpha pragmeme, which will inhibit that pro carcinogenic progesterone metabolite when given together. Just like the body created all these checks and balances, you even see it in the metabolites.”
Dr. Goodyear refers to the work of Dr. John Wiebe on hormonal regulatory mechanisms. Dr. Wiebe is a professor at Western University’s Department of Biology.
He and his team identified two new types of steroid hormones produced in breast tissue from progesterone metabolites that “appear to have the ability to regulate all forms of breast cancer.” One hormone (5aP) is “cancer-promoting” because it stimulates tumor growth and metastasis. The other hormone (3aHP) is “cancer-inhibiting” because it “suppresses cell proliferation and detachment.”
Their studies found that both hormones “act on estrogen-responsive and estrogen non-responsive cells, as well as on tumorigenic and non-tumorigenic cells.” The results “strongly suggest” that these steroid hormones “may have the capacity to regulate all forms of breast cancer,” depending on the ratio of 5aP and 3aHP in the breast tissue microenvironment.
Dr. Goodyear concluded, “This brings full perspective that progesterone metabolism is complex, but then how that’s interacting with lots of other hormones, is complex, and how there’s this cross talk and cross-regulation and cross-communication at the level of the hormones, at the level of the metabolites, and at the level of the receptors.”
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