Can a imbalance in progesterone cause breast cancer


Does progesterone increase breast cancer risk?

Unlike studies of other oral contraceptives, studies indicate that progestin-only formulations do not increase the risk of breast cancer, although the literature is hampered by small sample sizes. Future research is needed to corroborate these findings, as further understanding of synthetic progesterone may initiate new prescription practices or guidelines for women’s health.

How does progesterone protect against breast cancer?

progesterone induces the maturation of glandular breast tissue (it’s undifferentiated tissue that’s much more susceptible to cancer) progesterone downregulates (suppresses) estrogen receptors in breast tissue.

Can Prempro increase risk for breast cancer?

Using Prempro may increase your risk of cancer of the breast, uterus, or ovaries. Talk with your doctor about this risk. Estrogen lowers the hormone needed to produce breast milk and can slow breast milk production. Tell your doctor if you are breast-feeding.

Can bioidentical hormones cause breast cancer?

The research on bioidentical hormones varies, and there are no conclusive findings on the impact of bioidentical hormones on the development of breast cancer. Estradiol and progesterone often have opposing effects on the development of cancer and other health outcomes, which are reflected in the studies on bioidentical hormones as well.


How is oral progesterone destroyed?

Oral progesterone is mostly destroyed in the gastrointestinal tract before it enters the blood circulation and delivered to the tissues. Based on saliva and capillary blood progesterone levels, topically delivered progesterone is 20-100 times more efficiently delivered to tissues. Studies in humans have shown that physiological amounts of progesterone (20-50mg) administered topically deliver physiological amounts progesterone to the breast tissue and suppress estrogen-stimulated cell proliferation (Chank KJ et al Fert Sterility 63: 785-791, 1995 and De Boever et al Endocrinol of Cystic Breast Disease, 1983). My concern is that women using estrogens and ORAL progesterone as hormone replacement may not be getting enough progesterone to tissues to counter the growth-promoting effects of the estrogens. Unfortunately, the estradiol level, relative to progesterone (i.e. progesterone/estradiol ratio), was not evaluated in these studies. In vivo, during the luteal phase of the menstrual cycle, the level of progesterone is approximately 100-200 times higher than estradiol in all body fluids that have been studied (serum, capillary whole blood, saliva, urine). Lower levels are associated with increased risk for benign breast disease, higher proliferative rates, and increased breast cancer risk (Sitruk-Ware et al J Clin Endocrino Metab 44, 771, 1977; Micheli et al Int J Cancer 112, 313-318, 2004).

What is a progestogen?

First, I think it important to define a progestogen; it is any molecule with a structure similar to the natural hormone progesterone that binds to and activates intracellular progesterone receptors. This would include all forms of synthetic progestins in addition to natural progesterone.

Does oral progesterone raise progesterone levels?

Oral progesterone therapy only raises progesterone to sub luteal levels (1-5ng/ml) (Nahool and Levits references) and this is also reflected in lower salivary and capillary whole blood progesterone levels. Luteal levels of progesterone (>10ng/ml) need to be achieved for progesterone to act as an estrogen antagonist to prevent estrogen from excessively stimulating breast cell proliferation. Women who have an excess of estrogen relative to progesterone (low progesterone/estradiol ratio), are more likely to have atypical benign breast disease that is at increased risk of developing into breast cancer (Sitruk-Ware et al J Clin Endocrinol Metab 44, 771, 1977). Low endogenous luteal progesterone levels in premenopause women (much more prevalent in peri-menopausal woman) have also been associated with increased breast cancer risk (Micheli et al Int J Cancer 112, 312-318, 2004).

Does progesterone cause breast cancer?

It is being suggested that progesterone increases breast cancer risk, contrary to popular thinking that this hormone is safe and helps prevent breast cancer. The following is my argument in favor of natural progesterone as a preventative for breast cancer, with reference to the Fournier studies that address this issue.

Does Fournier study look at progesterone alone?

It is important to also keep in mind that the Fournier studies did NOT look at the effect of progesterone alone, or compare the effects of oral vs topical progesterone. Most of these studies are based on oral progesterone use.

Does topical progesterone deliver to tissues?

When it is finally realized that topical hormone deliver of progesterone is a very efficient way to deliver progesterone to tissues, and that serum is not reflective of this delivery, progress will be made in avoidance of over-treatment (often occurs with topical delivery as a result of tracking success with serum levels that do not increase significantly), and delivery of a physiological amount of progesterone to tissues that is breast protective. Dr. John Lee, and many of those who follow his protocols for physiological delivery of topical progesterone have reported very few breast cancer cases in their clinical practice. While this is an anecdote, their use of topical progesterone in physiological amounts deserves more attention by the medical establishment.

Is progesterone protective?

This is entirely consistent with the notion that when progesterone is delivered topically at a physiological level, it is protective. When I talk to very high levels of people about why they should at least study the relationship of topically delivered progesterone to breast cancer risk, I am told they don’t think it could possibly be effective …

Why is progesterone used in contraception?

Orally administered progesterone has limited biological effects because it is poorly absorbed, even in micronized form, and is metabolized extensively during the hepatic first pass. For this reason and because more potent progestational compounds were needed for effective antifertility treatment, progestins were developed. A variety of progestins are now available not only for contraception, but also for menopausal hormone therapy to prevent endometrial hyperplasia and lessen the risk of endometrial cancer in estrogen-treated postmenopausal women. The progestins can be classified, based on their chemical structures, as those related to progesterone (C-21 progestins) and those structurally related to testosterone (C-19 progestins) ( 16 ). An example of a C-21 progestin is medroxyprogesterone acetate (MPA), whereas norethindrone (norethisterone) and levonorgestrel are C-19 related progestins ( Fig. 2 ). Differences in pharmacologic properties of progesterone and some of the commonly used progestins are summarized in Table 1.

What is the role of estrogen in breast development?

Much of what is known about breast development has been derived from studies of rodents, which provides a useful, albeit imperfect, model for breast development in women. The breast develops at puberty with the establishment of menstrual cycling ( 17, 18 ). Estrogen and progesterone are sequentially involved in pubertal breast development primarily via a paracrine mechanism ( 19–21 ). Specifically, in vivo studies of hormonal ablation via ovariectomy and subsequent hormone replacement suggest that estrogens drive the first stage of pubertal development in the breast, whereas both estradiol and progesterone are responsible for cellular proliferation in the mammary gland (reviewed in ( 22 ); references to “mammary” gland throughout this manuscript refer to animal model data). Cell proliferation in the mammary epithelium ceases in ovariectomized mice; however, reintroduction of estradiol is sufficient to induce epithelial cell proliferation and restores ductal outgrowths consistent with intact pubertal animals. Estradiol alone is not sufficient to induce mammary gland cellular proliferation in pregnant animals ( 23 ). Similarly, progesterone is not sufficient to stimulate cellular proliferation in the absence of estrogen, as demonstrated by experimental studies conducted in ovariectomized mice showing that PR expression in mammary epithelium is dependent on interactions of estrogen with ERα to induce PR transcription ( 24–26 ). As is emphasized throughout this review, progesterone acts primarily through a paracrine mechanism, which makes cell culture experiments challenging. We are not aware of any co-culture systems for luminal progenitor cells that enable testing amplification of paracrine progesterone signaling. Further, progesterone’s paracrine signaling makes clinical translation a challenge as well, given that levels of other circulating hormones/growth factors and their cognate receptors likely influence the response to or effects of progesterone.

What are the lobules of breast cancer?

Breast lobules are microscopic structures that represent the main source of breast cancer precursors and with aging these structures undergo simplification and obsolescence ( 33 ). Studies of women who have undergone benign breast biopsies demonstrate that reduced levels of TDLU involution are associated with increased breast cancer risk, independent of other breast cancer risk factors ( 32, 114, 115 ). Analyzing the association between serum hormone concentrations among premenopausal women and levels of TDLU involution of normal breast tissue donated for research demonstrated that higher progesterone levels in the luteal phase were associated with fewer lobules per unit area [odds ratio (OR) 0.80, 95% confidence interval (CI) 0.72–0.95; p<0.0001] ( 116 ). However, this analysis was based on 237 premenopausal women whose samples were evaluated with chemiluminescent immunometric assays, which may lack the sensitivity and specificity of newer LC-MS/MS assay methods ( 117 ). In the same study ( 116 ), analyses of postmenopausal women were limited by a smaller sample size (n=148) and low assay sensitivity (large number of samples below assay detection limit), which precluded quantitation.

What are the genes that cause cancer?

Pathogenic mutations in DNA repair genes such as BRCA1, BRCA2, CHEK2, PALB2, ATM, P53 and others are associated with elevated risk for breast cancers. While some gene mutations are linked to triple negative breast cancers (eg, BRCA1) others are linked to ER+ breast cancer (eg, CHEK2 ). The developmental and mechanistic origin of these tumors are poorly described in the literature. A recent study that investigated BRCA1 mutation carriers concluded that BRCA1 mutation could drive aberrant luminal progenitor expansion independent of progesterone ( 130 ). A more recent study from the same group has shown that BRCA1 mutation carriers have deregulated progesterone signaling leading to higher proliferation and DNA damage in a progesterone-sensitive RANK+ luminal progenitor subset ( 111 ). An independent study of BRCA1 mutation carriers observed that luminal progenitors displayed an aberrant differentiation program but failed to find expanded luminal progenitors in their samples ( 131 ). Furthermore, data from a mouse model provided evidence to suggest that aberrant expansion of BRCA1 null luminal progenitor is linked to the replication-stress associated DNA damage response, where proliferation of mammary progenitors is perpetuated by damage-induced, autologous NF-κB signaling ( 112 ). There are other functions of BRCA1 relevant to genomic stability that are compromised in patients carrying a deleterious mutant allele of this gene. Recent studies show that haploinsufficiency of BRCA1 leads to accumulation of R-loop, a DNA-RNA hybrid structure associated with transcriptional regulation and genomic instability in luminal progenitors ( 104 ). Chromosomal aberrations have been associated with mammary progenitors in BRCA1 insufficiency as well as experimental models of human mammary progenitors mimicking loss of BRCA1 function ( 132, 133 ). Together, human and murine studies provide credence to the notion that the origin of BRCA1-mutation associated triple negative breast cancers is in the ER- luminal progenitors. Such detailed examination of cancer risk mechanisms at the level of cellular differentiation is simply not available for other DNA repair genes.

Why are antibodies needed for breast cancer?

Better antibodies are needed to detect PR isoforms and cell systems to capture paracrine signaling events. Advances in these areas will provide a broad spectrum of exciting new discoveries that will improve not only the biologic understanding of progesterone in breast cancer, but also the clinical relevance.

Which hormone is involved in pubertal breast development?

Estrogen and progesterone are sequentially involved in pubertal breast development primarily via a paracrine mechanism

Does estrogen affect breast development?

With respect to hormone receptor signaling, estradiol and epithelial ERα signaling are necessary for ductal elongation during early puberty ( 52–54 ); further, it has been demonstrated that progesterone/PR are not necessary for this stage of early breast development ( 55 ). Increased estrogen levels induce PR expression; this is known as ‘estrogen priming’ and is common to most progesterone target tissues. PR signaling by progesterone is required in the epithelial compartment for side branching and alveologenesis ( 28, 55–57 ). Recent studies demonstrate different roles of PR-A and PR-B in estrogen signaling and ER chromatin binding ( 58–60 ). More specifically it has been demonstrated that PR-B is uniquely required for the latter stage of breast development (ie, side branching and alveologenesis) ( 35, 36 ). Thus, as the mouse reaches maturity, cyclic progesterone exposure results in ductal development and dichotomous branching that fills the mammary fat pad. During pregnancy, progesterone signaling via PR and prolactin signaling via the prolactin receptor (PrlR) in the epithelial compartment are required for branching and alveolar proliferation and differentiation ( 61, 62 ).

What Does Progesterone Do?

But it’s not just about baby-making. There are many research studies that show the protective role progesterone plays in the body. It protects against hypertension, lowers blood fats , protects nerves, and prevents coronary hyperactivity (a sign of coronary artery disease) and helps with hot flashes, night sweats, insomnia, and anxiety. There is also evidence that is may be protective against cancer.

What is bio-identical progesterone made of?

Bio-identical progesterone is made from a compound found in wild yams (diosgenin ). This compound is altered in the lab to be identical to what your body produces. Your body cannot make this conversion on its own, so wild yam cream is not effective. Bio-identical products are available in creams, oils and oral capsules.

How much more likely is breast cancer in women in the placebo group than in the two drug group?

The results showed that women in the two-drug group were 24% more likely to develop breast cancer than women in the placebo group. However, women in the estrogen-alone group did NOT have an increased risk (and in fact the, the trend was toward reduced risk).

Can estrogen replacement cause cancer?

We know that estrogen replacement (HRT) given without progesterone to women who still have a uterus causes endometrial cancer. Studies published in 1995 found that women who had been exposed to HRT for longer than 5 years had a 32% increased risk of getting breast cancer.

Can progesterone be used for cancer patients?

I am not aware of any large-scale clinical trials looking specifically at progesterone use in patients who have had hormone-sensitive cancers. As with many therapies, it’s important to assess risk vs. benefit (including quality of life issues). Any woman who has a history of cancer should discuss the use of any hormonal therapy with her care team.

Does progesterone cause cancer?

It’s also why some states require labeling on progesterone that suggests that natural progesterone products may increase the risk of cancer.

Is estrone a carcinogen?

He concludes that “the evidence is strong that unopposed estradiol and estrone are carcinogenic for breasts, and both progesterone and estriol, the two major hormones throughout pregnancy, are protective against breast cancer.”.

Which hormone is more likely to cause breast cancer?

Co written with Dr David Zava, a biochemist and breast cancer researcher, the pair found that: Women with low progesterone levels and estrogen dominance are more likely to get breast cancer and have poorer treatment outcomes.

What happens when progesterone levels are brought up to normal?

When progesterone levels are brought up to normal, healthy levels, this turns on genes that are able to prevent breast cancer, as well as reducing the size of existing tumors. Dr Lee had 3 rules for bioidentical hormone therapy [3]:

What is PR+ in cancer?

When it occurs, this is known as ER positive (ER+) and PR positive (PR+) breast cancer, and these types of cells have been deemed to have better treatment results than tumors that do not have these receptors. This is how they work. Estrogen and progesterone receptors are found in many of the cells of our bodies, including the breast.

What happens when estrogen and progesterone are in contact?

What occurs is that when an estrogen or progesterone molecule comes into contact with its respective receptor, the molecule docks with the receptor and activates it. When this happens, the receptor enters the nucleus of a cell and attaches to specific places on chromosomes that contain all of that cell’s genetic coding, in effect turning on or off specific genes that govern the behavior of that cell. This effect happens constantly – if the body has enough estrogen and progesterone to activate the receptors.

Why do women have estrogen dominance?

The main factors for this are poor diet, rising obesity levels, stress, lack of exercise, xenoestrogens in the environment (mainly caused by hormone-altering chemicals), all of which are causing many women to suffer from estrogen dominance.

What happens when estrogen receptors are activated?

This reprogrammed the estrogen receptors to cease turning on genes that promote cancer cell growth. Instead, the receptors turned on genes that promoted apoptosis (cancer cell death) and promoted growth of normal, healthy cells.

Where are estrogen and progesterone found?

Estrogen and progesterone receptors are found in many of the cells of our bodies, including the breast. They are the mechanism by which hormones (chemical messengers) are allowed to change the behavior of cells. Once hormones have docked with the cells via the receptor sites, they can change how particular tissues and organs function.

How does progesterone help cancer cells?

How progesterone helps breast cancer cells evade the immune system. August 03, 2020. Seven out of 10 breast cancer cases are hormone-receptor positive, meaning the cancer cells grow in response to estrogen and/or progesterone. The link between these hormones and breast cancer has been known for decades, and scientists continue to explore this …

What is the role of progesterone in women’s menstrual cycle?

Produced primarily in the ovaries following ovulation each month, progesterone plays an important role in a woman’s menstrual cycle and pregnancy. It’s a common misconception that once …

What hormones are no longer present during menopause?

It’s a common misconception that once a woman reaches menopause, sex hormones like progesterone and estrogen are no longer present in the body. It is true hormone levels decline, but they are still present, and the source of the hormones change.

How do estrogen and progesterone work together?

Estrogen and progesterone work in tandem the former hormone helps cancerous cells flourish while the latter tricks the immune system. Our ever-watchful immune system flags and constantly removes tiny tumors from our body, often thwarting the development of cancer. This checks and balances function of the immune system is a critical element …

Why are breast tumors immune cold?

“We hypothesize that one reason breast tumors are immune-cold is because progesterone is inhibiting the immune system’s ability to do its job ,” Dr. Hagan said.

Why are checkpoint inhibitors given to cancer patients?

Immune checkpoint inhibitors are given to patients to reawaken their immune system and effectively fight off the tumor cells. Some types of cancers, like skin cancer and lung cancer, respond more favorably to immune checkpoint inhibitor treatment than others. Others, like breast tumors, are “immune-cold,” meaning they don’t provoke a strong response by the immune system and subsequently don’t respond well to this type of treatment.

Does estrogen cause breast cancer?

Dr. Hagan added that cancer may start developing while a woman is transitioning to menopause and producing a mid-range level of hormones. Estrogen’s role in breast cancer growth is already well-understood, and there are several approved treatments to target the hormone. But that’s just half the story.

What are the causes of breast cancer?

One of the most significant factors is synthetic hormone replacement therapy (HRT), specifically estrogens. There are similar risks for younger women who use birth control pills, which are also comprised of synthetic hormones, and have been linked to both cervical and breast cancers. Still, each of us are increasingly exposed to estrogen-like compounds called Xenoestrogens. “Estrogen pollution” is present everywhere, from plastics to canned food and drinks, food additives, household cleaning products and pesticides. And, estrogen levels are rising in our waterways as a result of the runoff from factory animal farms.

Why is estrogen in water rising?

And, estrogen levels are rising in our waterways as a result of the runoff from factory animal farms. When researchers analyzed the risk of breast cancer in women under age 51, those with the highest progesterone levels had a staggering 70% decreased risk compared to the group with the lowest progesterone levels.

Does progesterone affect breast cancer?

When researchers analyzed the risk of breast cancer in women under age 51 , those with the highest progesterone levels had a staggering 70% decreased risk compared to the group with the lowest progesterone levels. For women diagnosed with breast cancer, findings from two other studies revealed that survival rates were strongly correlated with the patient’s progesterone levels at the time of surgery. The scientists concluded: “This study has confirmed that a raised level of progesterone at the time of tumor excision is associated with an improvement in prognosis for women with operable breast cancer.”


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