How Does Progesterone Support Cancer Treatment?
Out of all the steroid hormones, progesterone is the most powerful anti-cancer hormone.
It has the ability to anesthetize cells, meaning it essentially ‘puts them to sleep’ by stopping division. While synthetic progestins increase cancer risk, natural progesterone is extremely protective against cancer, primarily because of its ability to inhibit cell growth.
Use of progesterone has been linked to lower rates of uterine and colon cancers, and may also be useful in treating other cancers such as ovarian, melanoma, mesothelioma, and prostate. Studies investigating the anti-cancer effects of progesterone conclude that progesterone is protective and preventative of breast cancer.
Progesterone can induce cancer cell death.
Progesterone regulates various cancer cell processes, including proliferation, apoptosis (programmed cell death), angiogenesis (blood vessel growth to tumors), and autophagy.
In clinical practice, progesterone has been used as a therapy for patients with endometrial cancer as well as for those with recurrent disease.
It works by inducing apoptosis, or programmed cell death. Progesterone can block cancer cells from moving through the cell cycle, specifically at the checkpoint between the G1 phase (the stage where a cell grows and prepares its machinery) and the S phase (the stage where it copies its DNA in order to divide). By stopping cells at this critical transition, progesterone prevents them from multiplying.
Research has also shown that progesterone can trigger apoptosis in beta-hCG–responsive tumor cells.
Progesterone can restore normal tissue function.
In some cases instead of killing cells, progesterone can push cancer cells into senescence, which is a state of permanent growth arrest.
When this happens, the cells remain alive and metabolically active, but they’re “frozen in time,” unable to divide. Unlike apoptosis, where cells are dismantled and removed, senescent cells stay in the tissue. This can be really beneficial in cancer because stopping uncontrolled division helps restore tissue to a more normal state, without the collateral damage that many conventional anticancer agents cause to healthy cells. In some cases, the immune system may later clear these senescent cells, but the key point is that progesterone’s effect is more about switching off the cell’s ability to multiply than forcing it into immediate death.
Progesterone:
- Induces cellular differentiation. It encourages cancer cells to mature into more specialized, less aggressive forms.
- Inhibits cell proliferation. Progesterone slows down the rate at which cancer cells divide, partly by suppressing growth-promoting genes like cyclin D1 and MYC.
- Reprograms estrogen receptor activity. It alters how estrogen receptors bind to DNA, reducing estrogen’s tumor-promoting signals in ER+/PR+ cancers.
- Promotes apoptosis. It triggers programmed cell death by upregulating p53 and downregulating survival genes like BCL-2.
- Improves mitochondrial function. It supports cellular energy production and reduces oxidative stress by enhancing mitochondrial efficiency and promoting a shift away from glycolysis toward oxidative phosphorylation.
- Reduces inflammatory signaling. It suppresses inflammatory mediators like IL-6, COX-2, and TNF-α, which contribute to tumor growth and immune evasion
- Stabilizes the tumor microenvironment. It helps maintain tissue integrity and reduce oxidative stress, creating a less favorable environment for cancer growth.
It’s important to note that synthetic progestins (like medroxyprogesterone acetate) are fundamentally different from natural progesterone. While they bind to the progesterone receptor, which is how they get their name, they do not mimic the biological actions of natural progesterone and can produce very different, sometimes opposing, effects.
Much of the confusion around progesterone in cancer comes from studies that used synthetic versions. Progestins are the ones historically associated with increased breast cancer risk in large studies.
Despite promising evidence from lab studies and small clinical trials, progesterone is not a common course of treatment in cancer.
One major reason is that natural progesterone is not patentable, which means pharmaceutical companies have little financial incentive to fund the kind of expansive, expensive trials required to shift medical guidelines. Instead, most of the research, and the guidelines that follow, are based on synthetic progestins, which behave very differently in the body.
As we continue to learn more about how hormones influence cancer behavior, it becomes increasingly clear that lumping natural progesterone together with synthetic progestins is a scientific and medical misstep.
“Physicians should have no hesitation prescribing natural progesterone” (Lieberman and Curtis, 2017).