It has been very commonly stated that progesterone supplementation is not harmful and that it does not cause problems. This is simply not true. Here is the evidence:
Progesterone Signaling and Uterine Fibroid Pathogenesis; Molecular Mechanisms and Potential Therapeutics 2023 Apr 9
https://pmc.ncbi.nlm.nih.gov/articles/PMC10136461
Note, this was published, 2023.
They list 5 mechanisms of action for how progesterone increases fibroids.
- “Studies demonstrated that progesterone signaling promotes the growth and proliferation of fibroid cells through increasing proliferating cell nuclear antigen (PCNA) expression, which increases both the number of fibroid cells and the size of fibroid tumors [39].”
- Apoptosis, or programmed cell death, is a mechanism by which abnormal or damaged cells are eliminated from the body. Progesterone has been shown to suppress apoptosis in fibroid cells, which may contribute more to the growth of UFs via B-cell lymphoma- (Bcl-) 2 protein expression induction [48] than myometrium [49].
- Cytokines are signaling molecules that play a significant role in the regulation of fibroid growth. Progesterone has been shown to modulate the production of cytokines such as TNF-α and IL-6 [54].
- The findings of Liu et al. suggested that DNA methylation and MED12 mutation together constitute a complex regulatory network that affects progesterone/PR-mediated RANKL gene expression, with an essential role in activating stem cell proliferation and fibroid tumor development [56].
- Since the formation of new blood vessels is vital for the delivery of nutrients and oxygen to the growing tumors [60], progesterone may promote angiogenesis through the upregulation of VEGF which stimulates the growth of blood vessels [61].
- ECM is an intricate network composed of an array of multidomain macromolecules organized in a cell/tissue-specific manner that provide structural support to cells [64]. In fibroids, the ECM is abnormal and may contribute to the growth and maintenance of the tumors. Additionally, progesterone signaling leads to the upregulation of matrix metalloproteinases (MMPs) which are involved in ECM remodeling [65].
My view is that the reasons why these issues are complex, and difficult to figure out is that there is a significant difference between the body making hormones naturally, verses taking them as supplements. Hormones are said to be “signaling hormones”.
Well, what if the hormones need essential building blocks like enough copper, zinc, iodine, etc., just in order to make them naturally? What if the signal is meant to be something like “we have enough copper, zinc, and iodine for growth”? What if, when we take hormones without the underlying minerals, the signal is thus no longer valid, because the underlying minerals are not present to make the hormones that signal growth? Then abnormal growth (without copper/zinc/iodine) such as growth of tumors, is the result.
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