Progesterone in Women #2- What You Must Know and Document Before Prescribing Menopausal Hormones

Progesterone in Women #2- What You Must Know and Document Before Prescribing Menopausal Hormones

What You Must Know and Document Before Prescribing Menopausal Hormones

Safety of P4 vs Progestin 

A recent review article published in JAMA made the distinction between estrogen-alone and estrogen with a progestin. Although the increased risk of breast cancer incidence is small with the use of a progestin, most literature proves an increased risk when a progestin is used, whereas there is a reduced risk for breast cancer with estrogen-alone. In women that did not have a uterus, then a progestin was not indicated as the reason for adding a progestin was to protect the uterus against estrogen induced endometrial cancer from unopposed estrogen stimulation. So, no uterus = no need for a progestin = no breast cancer risk. There was no mention or suggestion in the JAMA article for the use of micronized progesterone as a safe alternative to a progestin. Although the current ACOG/NAMS guidelines do mention that micronized P4 could be an alternative to the use of a progestin there is no mention of the safety and efficacy of P4 that would make P4 the logical treatment of choice. Why is that?  

Should P4 Replace the Use of Progestin 

Last week at the Annual Academic Summit I presented all the data that estrogen (CEE or E2) reduced the risk and incidence of breast cancer in RCTs. However, weaker powered (Grade C & D evidence) observational studies showed a possible risk of breast cancer with long-term estrogen-alone use. However, this risk was neutralized with progesterone (P4) with an RR of 0.8 to 1.0. There always appears to be a protective effect of P4 as I cannot find any supporting literature where P4 increases breast cancer risk. OB/GYN Management published a meta-analysis where the relative risk of P4 was 1.0 whereas MPA was 1.7 and norethindrone was 2.1. And the reason we do not recommend P4 over any progestin is? If the literature and studies prove identical endometrial protection as with any progestin and without the side effects and complications of progestins, then why is P4 not recommended and used preferentially over any progestin? Am I missing some literature proving that progestins are safer than P4? Or that P4 is somehow harmful and should not be used? What is it in the medical literature that I/we/they are missing thereby allowing for their verbiage that P4 could be an alternative as opposed to “should be” the alternative that replaces the use of any progestin?  

Progestins Increase the Risk of Many Diseases Including Breast Cancer, CAD, MI, CVD etc. 

Progestins have been proven to increase the risk and incidence of breast cancer, CAD and MI, CVD and CVA, blood clots, dementia and Alzheimer’s, diabetes, dyslipidemia, and depression. P4 does none of the foregoing. Other than both medications protecting the uterus against endometrial proliferation, they are completely divergent in their side effects, problems, and complications. The current guideline verbiage suggesting that P4 could be an alternative begs for an explanation as to why anyone would contemplate the use of any progestin with the associated side effects, problems, and complications when a safe and efficacious alternative exists (P4) without any progestin side effects, problems, or complications. When would a progestin ever be used preferentially over P4? 

E2 Plus P4 Used together Reduce Endothelial dysfunction and Plaque Formation Beyond E2 Alone 

At the WLM Summit last weekend I presented studies where E2 reduces foam cell formation and plaque. The addition of P4 to E2 further reduced foam cell formation well beyond that of E2 alone. Both hormones show synergism when used together to reduce endothelial dysfunction and plaque formation. Brain studies showed the same benefit of adding P4 to E2. E2 was beneficial in reducing beta-amyloid protein and hypometabolism in neurons. Addition of P4 furthered the benefit of E2 whereas addition of MPA negated estradiol’s benefit on protecting against Alzheimer’s disease and neurodegenerative disease. Again, great synergism was seen when P4 was added to E2 whereas use of a progestin negated estrogen’s benefit in heart, brain, breast, and other tissue. Progestins were proven to be harmful to breast, brain, and heart tissue. It is amazing that progestins are still produced by pharmaceutical companies and that these drugs are still promoted by our OB/GYN medical societies.  

Criticized for Prescribing P4  

Despite the positive effects of P4, it is amazing the times that I have been criticized for prescribing P4. It has been standard operating procedure (SOP) for me to be told by my HRT (Hormone Replacement Therapy) patients that their doctors state that I do not know what I am doing because I prescribed P4 to patients that have had hysterectomies. Now I invoke the assistance of the patient to decide in their care. My patients are quick to tell me the derogatory and demeaning comments my patient’s PMDs use to discredit and demonize me. I use the medical literature to guide therapy as well as allow the patient to understand why we do what we do despite the negativism voiced by our peers against the use of bioidentical hormones. A common criticism that I have heard and dealt with for 25 years is the use of P4 in menopausal women that have had hysterectomies. “Mrs. Smith, I understand that your doctor does not understand why I prescribed P4 for you because that is the way that they and I were trained. The most common reason for prescribing progesterone was to protect against uterine cancer, and you can understand their reasoning for not using P4 if you do not have a uterus. However, there are many other benefits of P4 besides protecting the uterus. Not taking P4 will prevent you from reaping all the other benefits of P4 if you do not take it. So, I will let you decide if you want to listen to your doctor, or to me” . True, you do not need MPA, however, you definitely need and would benefit from P4.”  

“Mrs. Smith, the most common and feared cancer in women is breast cancer. If you don’t want to protect against breast cancer, and your doctor does not want to protect you against breast cancer, then do not take progesterone. If you do not want to protect against CVD or neurodegenerative disease, or your doctor does not want to protect you against CVD or NDD, then do not take progesterone. On the days that you do not want to protect your brain, breasts, heart, blood vessels and bones, then don’t take progesterone. It is the science and literature that should guide our practice of medicine. “Mrs. Smith, just because you do not have a uterus does not mean that you do not need progesterone or that you would not benefit from using P4. Most women commonly state that they sleep and feel much better on P4 due to sleep enhancing benefits by stimulating GABA receptors. Menopausal patients frequently claim that they love their progesterone, meaning that they sleep and feel better with less depression and anxiety. P4 also treats and prevents hot flashes and night sweats. OBJECTIVES: 

  1. Review current and pertinent literature as to the many benefits of micronized progesterone beyond just protecting the uterus.  
  2. Recognize the confusion in terminology of P4 and MPA and the medical literature demonstrating the significant differences between both. 
  3. Describe the harm of synthetic progestins (MPA) in contrast to micronized progesterone (MP). 
  4. Discuss the many health benefits of P4 thereby making hysterectomy inconsequential as to the use of P4 in all menopausal women.  
  5. Explain the concept of breast protection as well as a breast cancer treatment by P4 administration. 


Despite your 58 y/o menopausal patient feeling much better on BHRT, she requests consultation based on a recent poor encounter with her PMD gynecologist. The PMD voiced concerns over the use of progesterone in patients that did not qualify for the use of progesterone due to the history of a hysterectomy. The patient was concerned after a confrontation with her gynecologist who felt that bioidentical hormones do not protect against breast cancer whereas they would increase the risk of cancer equally to that of SHRT. The PMD gynecologist was adamant that hormones can increase the risk of cancer and that the patient should stop taking P4 due to the risks and the fact that it is definitely not indicated in a patient with a history of a hysterectomy. You reassure your patient that there are differing opinions on hormones and that you will provide her with a series of articles that demonstrate the many benefits of P4 and lack of any harm in any study. You politely explain the discrepancy in thought and understanding of hormones. The patient appreciates your experience and explanation but also in the medical literature and studies supporting the safety and efficacy of micronized P4 in contrast to MPA, which is the point of misunderstanding of the PMD gynecologist. 

Respectfully submitted,

Neal Rouzier