In the first part of this article, the different roles of natural progesterone with regard to the brain, thyroid gland, bone health, and heart health were discussed. This overview continues with the main role of this incredible hormone in this second part.

Progesterone and the breasts

With the near-epidemic increase in breast cancer, if there is one tissue that women are most worried about, it would be the breast tissue! Everything that protects it automatically takes on a highly precious aura! You will not be surprised to learn that natural progesterone supports the health of this tissue.

Progesterone prevents the excessive proliferation of cells in the breast tissue. Indeed, estrogen stimulation not compensated by progesterone promotes breast diseases including cyst formation, the swelling that is accompanied by the menstrual cycle, and cancer. According to the results of a meta-analysis of 86,881 postmenopausal women, the use of natural progesterone is reported to be associated with a significantly lower risk of breast cancer compared to synthetic progestins. Lack of ovulation and low serum progesterone levels have been associated with a significantly higher risk of breast cancer in premenopausal women. The use of natural progesterone is also linked to lower rates of uterine and colon cancers and may also be useful in the treatment of other cancers such as ovarian, melanoma, mesothelioma, prostate, and thyroid. (19-22)

In addition, a deficiency in progesterone would contribute to increasing the number of tumor growth factor receptors and would represent a risk factor linked to breast cancer. (23) We also know that natural progesterone downregulates the formation of metalloproteinases; enzymes required by cancer cells to enhance their invasive capacity. (24-26)

The majority of breast cancers contain both estrogen and progesterone receptors (called ER-positive/PR-positive tumors or hormone-dependent cancers). This type of cancer gets better outcomes from treatment. What are estrogen and progesterone receptors and what exactly do they do? It was a scientific team affiliated with the UK Cancer Research along with the University of Adelaide in Australia that shed light on this major point. (27)

Hormone receptors are transcription factors, meaning they are both involved in turning genes on and off in cells. They represent the mechanism that allows estrogen and progesterone to modify the behavior of our cells. Breast cancer cells have an increased sensitivity to estrogen. Once estrogen binds to its receptor on the cell surface, it activates and enters the cell into the nucleus, where it binds to specific regions of DNA. This binding activates the transcription of a group of genes (including Bcl-2) that promote cellular division and therefore, potentially, tumor growth, but also deactivates other genes involved, among others, in cellular death. This reprogramming is central to the tumor process and its treatment with hormone modulators such as Tamoxifen, Femara, Arimidex, and Zoladex.

The progesterone receptors have, on their side, an astonishing action. When activated by this hormone, they bind directly to estrogen receptors and inhibit the activation of genes that promote cellular growth in addition to activating genes (including p53) that promote cancer cell death (apoptosis) and the growth of healthy, normal cells! (28) The researchers found that the estrogen receptor binds to different regions of DNA depending on whether or not progesterone is present, and concluded that the involvement of progesterone was crucial to ensure a safe environment.

This same observation was observed in mice expressing hormone-dependent cancer. The research team found that tumors in mice that received estrogen alone grew, compared with a decrease in size in tumors in mice that received both estrogen and progesterone. From there came the idea of ​​exposing the tumors to a combination of Tamoxifen and natural progesterone, and noticed a marked decrease in tumor growth compared to tumors treated only with Tamoxifen. (29)

Progesterone does two things. First, it can prevent healthy breast tissue cells from mutating into tumors. Second, it can limit the growth of existing breast tumors or even reduce them in size. These benefits are exclusively related to natural progesterone and not synthetic progestins which increase, rather than reduce, the risk of breast cancer. Thus, it can be concluded that if women have healthy progesterone levels, through natural progesterone supplementation, they could significantly improve their treatment outcomes.

Progesterone and the reproductive system

Progesterone acts strongly on the uterus: it allows the establishment of an environment favorable to reproduction. Its contribution to fertility is well documented and pregnancy cannot be foreseen in the absence of this hormone. It is also used regularly in assisted reproduction centers. The most compelling evidence confirming the difference between progestins and natural progesterone is that progesterone is frequently prescribed to maintain pregnancy and reduce the risk of miscarriage, whereas progestins are, in their case, absolutely contraindicated because they interfere with fertilization by thickening the cervical mucus, which is more dangerous for the fetus! (30, 31) Despite these differences in action, many doctors and researchers continue to believe that progesterone and artificial progestins are synonymous!

The more a woman advances in her thirties and forties, the more she feels the hormonal fluctuations which are characterized by a decrease in the ovulatory cycles and consequently of progesterone. A condition called luteal insufficiency is frequently encountered in pre-menopause. It means that the corpus luteum does not produce enough progesterone, despite normal ovulation. It is also possible to have anovulatory cycles due to the lack of development of the corpus luteum, where the egg is lodged. This is without the exclusion of women who use birth control pills, as they do not enjoy the benefits of progesterone throughout their contraception.

What is a progesterone deficiency like? This would be estrogen dominance. We owe this concept to Dr. John Lee. He was the first to mention that during peri-menopause, despite a drop in the overall production of hormones, the body remained, in the majority of cases, under an estrogenic rule caused by a marked decrease in progesterone. Dominance represents this gap. According to this doctor, this situation is detrimental since the main role of progesterone is to watch over the proliferative nature of estrogen. No wonder many of the symptoms that accompany progesterone deficiency are identical to those caused by excess estrogen. This does not mean that estrogens are dangerous in nature, but that their balance is synonymous with safety! Shorter cycles, heavy bleeding with clots, uterine fibroids, premenstrual syndrome, irritability, anxiety, insomnia, musculoskeletal and menstrual pain, heart palpitations, increased breast tenderness, constipation, bloating, abdominal distension and others are signs that appear with an increased need for progesterone.

Atypical endometrial hyperplasia is a precancerous condition that consists of excessive proliferation of abnormal cells. If left untreated, the risk of developing uterine cancer increases. Having anovulatory cycles represents a determining factor of this condition since it leaves estrogens unopposed. Treatment options include (what a surprise!) progesterone. (32)

I briefly mentioned the protective role of progesterone on endometrial (uterine) cancer. This cancer is the most frequent among cancers within the gynecological sphere. Early detection greatly facilitates treatment and ensures remission in 95% of cases. If the causes of cancer are always multifactorial, we note, all the same, that in 80% of cases estrogen dominance is apparent. (33) Indeed, its incidence is strongly associated with prolonged estrogenic action without being neutralized by progesterone. Since a high level of the latter interferes with the number of estrogen receptors and consequently opposes the cellular growth induced by estrogen, progesterone represents the main tumor suppressor of the endometrium. (33,34) Among the other risk factors, apart from genetic predisposition, we find overweight, arterial hypertension, and atypical hyperplasia, which are conditions sensitive to the action of progesterone!

Hormonal balance in a world saturated with endocrine disruptors

It is increasingly accepted that there is a direct link between environmental quality and hormonal balance. Certain molecules that we encounter every day have the ability to mimic our hormones by binding to their specific receptors. This phenomenon leads to a cascade of metabolic disorders and unpredictable consequences on our cells and on our entire organism. These usurping substances to which we are exposed bear the common name of endocrine disruptors or xenobiotics.

As defined by the European Union in 2002, endocrine disruptors are “substances which, by interfering with the functions of the hormonal system, risk negatively influencing the processes of synthesis, secretion, transport, action or elimination of hormones”. These molecules are suspected of being involved in the majority of cancers, infertility, allergies, autoimmune diseases, birth defects, increasing bacterial resistance to antibiotics, and others. (35) According to the European Commission, 99% of the more than 100,000 chemicals introduced into the environment over the past 70 years are still today under-regulated and therefore difficult to control. These endocrinotoxic saboteurs are all around us; in water and food, plastics, paints, furniture, detergents, textiles, and medicines, in addition to being concentrated in personal hygiene products and cosmetics.

A large majority of these disruptors mimic estrogen by interacting with the receptors for this hormone, which induces a direct action on estrogen-sensitive genes. Breasts, endometrium, brain, genitals, adipose tissue, and liver unfortunately represent target organs for these toxic molecules. Since they are chemically and clinically active, and we understand how much they can contribute to hormonal imbalance and accentuate estrogen dominance. There is definitely something to be concerned about! In a context so favorable to estrogens, progesterone is essential because of its protective and highly essential effects!

Progesterone plays an important role at all ages of a woman’s life and this remains true even during menopause. The fact that progesterone receptors are found far beyond the boundaries of reproductive tissues allows us to consider the important contribution of this hormone to overall health. The hormone of temperance and benevolence, it accurately contains the excesses of its sister, estrogen, while completing its essential functions. This partnership is essential to achieve the coveted hormonal balance. The estrogen dominance that characterizes hormonal instability in many women accentuates the risk factors for many conditions, impacting cognitive faculties, bone capital, breast health, and the cardiovascular profile, to name a few. Unfortunately, too many doctors have been trained to believe that synthetic progestins are actually progesterone and produce similar effects. This confusion is fed by quantities of publications that lack rigor only in the terminology used. It is high time to separate the information so that natural progesterone finally overcomes the weight of the disadvantages linked, for the most part, exclusively to synthetic progestins.

Article initially published in Vitalité Québec, February 2021

Véronique Bourbeau, Certified Naturopath





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