Progesterone in Women- What You Must Know and Document Before Prescribing Menopausal Hormones (Part 1)

by Neal Rouzier, MD

Unfortunately, I cannot cover every paper and every concept of every hormone in the WLM|APIM courses. There is so much more that I would like to cover, discuss, and teach but there is not enough time in the day. As a result, the webinar series was established to be a complement to that which is taught in the Part I BHRT Series Workshop. The first webinar series was on thyroid hormone and everything that you should know before prescribing thyroid. The next series reviewed testosterone for men and then for women, with all the important studies and concepts that one should know before prescribing testosterone as the concepts and guidelines are completely the opposite for men and women. Next, we will review the most forgotten, most misunderstood, and most important hormone which is just as important as estrogen (E2). However, its importance is not acknowledged by most medical societies. And based on the literature I’ll be presenting provides some of the best protection against the most common cancer in women, breast cancer. 

A Recent Malpractice Suit Against an OB-GYN

The impetus for this webinar involves a case that I had to defend which could easily have been lost were it not for my prior insight and experience with other cases. The plaintiff was suing an OB–GYN for damages that resulted from the patient developing breast cancer while on BHRT. (Note that the OB–GYN was NOT a WLM trained physician). The patient had been prescribed the usual BHRT which was taken for 2 years. A lump was discovered, and a positive mammogram led to the diagnosis of breast cancer. The plaintiff then sued the doctor, claiming failure to warn of the risk of breast cancer while on menopausal HRT. Everyone knows and understands the risk of breast cancer with estrogen and any progestin, i.e., CEE/MPA. However, the literature well supports that estrogen-alone does not increase the risk of cancer, natural progesterone (P4) does not increase the risk of cancer, and testosterone does not increase the risk of cancer. Plaintiff’s attorney hired 2 academicians that testified that both estrogen and progesterone increase the risk of cancer. My job was to prove the opposite, which I felt would be quite easy. I have stacks of papers proving that estrogen, progesterone, and testosterone either alone or together do not increase the risk of cancer. In fact, most literature proves that they protect against breast cancer and can be utilized to treat active cancer. This should be an easy straightforward case to defend against, but it wasn’t. And here’s the catch. There are two concerns/issues that all clinicians need to be aware of when prescribing BHRT to menopausal women. One comes before lightning strikes and a suit is filed. Secondly, what to do and what must be understood to prevent, defend, and win any case.  

Importance of Written Documentation for Consent

The most common mistake/error that clinicians make is failure to warn as well as the necessary written documentation of that informed consent. There is absolutely no data, study, or paper that proves estrogen (either CEE or E2) increases the risk of breast cancer. I presented the JAMA paper proving that estrogen is the only drug that decreases breast cancer mortality; AIs and tamoxifen don’t. The same applies to P4 whereby P4 prevents breast cancer and is used as a treatment for active breast cancer. So, if E2 and P4 protect against cancer, why does one have to inform the patient of the increased risk of cancer? Because that is the common belief, and some hired lawyer will testify against you claiming that hormones cause cancer and that there is no difference between CEE and E2 or between MPA and P4. In addition, the FDA and the PDR treat all hormones as if they are the same and that there is no difference from one to the next. If you look up Prometrium in the PDR, the verbiage for P4 is the same identical verbiage for MPA, which states an increased risk of breast cancer despite the paucity of studies that P4 doesn’t cause harm. The FDA required all manufacturers of E2 and P4 to use the same identical wording, risks, and harms as synthetic HRT. The pharmaceutical companies that manufacture SHRT are not prone to lawsuits because they have warned of the risks in the patient handout dispensed with every prescription for hormones. However, compounded BHRT does not come with the standard PDR handout, and it becomes the clinician’s responsibility to inform the patient and document that informed consent in a written note in the chart. Typed consents are worthless; it must be hand-written. Had the OB-GYN just written and documented the discussion, there would have been no case. However, there was no documentation of any discussion of risks in the patient’s chart, which means in the eyes of the court that it did not happen. The most common error/mistake in these cases is failure to warn and failure to document the informed consent in a hand-written note.  So, despite the lack of evidence proving BHRT increases the risk of breast cancer, we must lie to the patient and warn them of the increased risk of cancer, all because that is what is stated in the PDR. Even though it is not factual, we must inform the patient exactly what is stated in the PDR.  

Presenting the Evidence?

In my deposition, I presented a plethora of data and studies to prove the safety and efficacy of BHRT, particularly the decreased risk for breast cancer. Plaintiff’s experts presented no literature or studies, only their opinions which stated that there was no difference between the various hormones, and they all had the same identical risks for breast cancer. I easily proved everything that they claimed about BHRT causing cancer to be false. There was indisputable evidence that the experts’ claims were false and the harm of SHRT (CEE & MPA) does not apply to BHRT (E2 & P4). Paper after paper, study after study proved the safety and efficacy and lack of harm of E2 & P4. The defense attorneys were so confident in the literature presentation that they felt there was no merit to the suit and petitioned for summary judgement. Not only did the judge reject the summary judgement plea, but also refused to let me present any of the studies that I painstakingly organized into a 3-hour presentation proving that the BHRT prescribed did not increase the risk of breast cancer. The judge allowed me only to give my opinion and disallowed any presentation of medical literature which would be too time-consuming and too confusing for a lay jury to process and understand. So, then, that pits me (a non-specialist) against two hired-gun expert academicians that were well-published and well-respected university professors. There is no way that my non-expert opinion would hold up against expert OB-GYN and Oncology specialists. The only logical way out of this predicament was to settle. But we didn’t. And here’s why. 

How the Case Was Won

Having prior experience with court cases and these scenarios, I anticipated the judge’s response in preventing me from presenting studies to support our case. Therefore, the defense attorneys presented all my literature during the depositions of the experts where they had to comment on all the evidence and science that was contrary to their opinions and statements made in their original interrogatories. What was presented, stated, and discussed in their depositions was admissible. We had the experts read and quote from our literature (that I provided to the defense attorneys) that disagreed with their expert opinions. When the papers they were forced to read contradicted their own statements and opinions from their interrogatories, all they could state was that their opinions were contrary to all the studies. When they were forced to review articles from their own literature that proved them wrong, they lost credibility. How could they state and claim one thing when literature and science proved their opinions contrary to science? Even though we were prevented from presenting specific papers and science, the experts were forced to read aloud all the studies that I provided to the defense attorneys. Making them read these studies during their depositions is where they hung themselves. Had I not provided all the literature to the defense attorneys in advance to make the experts testify that their opinions were contrary to all the scientific literature, we would not have been allowed to present any of the literature that the judge rejected.  In my testimony, I could only give my opinion, but I continuously referred to experts’ testimony where they contradicted themselves and lost credibility. We proved that the plaintiff’s experts were not experts in hormone therapy or the current medical literature. Plaintiff’s attorney was livid.  

Protecting Yourself as a Provider

Appreciating the foregoing, what can/should we do to prevent the above scenario as history does repeat itself? If any information is included in the chart, it is admissible as evidence in any suit. If the chart does not contain any information, then it did not happen. I have been very impressed by one WLM physician who includes medical studies in the patient’s chart. He also sends the same papers to the patient with the intent to inform and educate the patient. And this applies to both men and women and for whatever illness or symptom they may have. For the above example, Dr. Rand will provide all the literature proving that estrogen, progesterone, and testosterone do not increase the risk of cancer. He will go on to provide literature where BHRT decreases the risk and incidence of cancer and is used as adjunctive therapy in treating active breast cancer. If these studies are included in the patient’s chart, it is all admissible as evidence and cannot be ignored or rejected. Plaintiff’s experts will have to discuss all the chart content, which they certainly would be hard pressed to refute. But this has to be done up front in order for the studies to be included as part of the medical chart, and therefore admissible as evidence.  

Properly written and documented informed consent coupled with medical literature support will provide protection against most litigation as well as provide confidence in that you are providing the best service and care for your patient. It should also be noted that by the time a breast lump is felt, the tumor has been present for at least 5 years, indicating that hormones did not cause the cancer to occur as the patient had been on HRT for only 2 years. The issue at hand was whether the hormones accelerated the growth of the tumor and whether the patient was informed of that risk, both verbally and in writing. We utilized the medical literature to prove that there was no harm from the BHRT prescription. The harm was the lack of documentation which this OB-GYN discovered the hard way. The appreciative doctor promised me that he would never let history repeat itself. 

Objectives:

1. Review studies demonstrating the biological activities of progestins are different than natural progesterone regarding cardiovascular and breast cancer risk. 
2. Demonstrate that P4 in long-term studies results in a RR of breast cancer from 0.6 to 1.0., in contrast to the RR of progestins to be 1.6 or greater. 
3. Contrast the negative effects on lipids with progestins in comparison with the synergistic effects of P4 with estrogen. (PEPI Trial) 
4. Realize that most studies prove harm with progestins whereas no study proved harm with use of P4, yet the risks are mistakenly stated to be equal as stated in the PDR.  
5. Discuss the anti-anxiety, vasomotor and sleep enhancing benefits of P4 in contrast to the depressive effects of progestins.  
6. Review studies whereby researchers commonly confuse terminology by using the term progesterone to describe a progestin thereby leading to false statements that progesterone increases the risk for CVD and breast cancer. The medical literature strongly suggests that P4 is both protective and preventive of breast cancer in contrast to progestins that increase the risk of breast cancer.  
7. List the many health benefits of P4 as well as the harm of anovulation and loss of progesterone which increases the risk of endometrial cancer, breast cancer, ovarian cancer, and heart disease.  

Case Presentation:

Your 58 y/o patient requests an appointment to discuss the use of BHRT that you have prescribed. Her friend recently developed breast cancer while taking BHRT which she finds very upsetting. In discussing the issue with her PMD gynecologist, she was advised that the risk of breast cancer is the same as that of SHRT. It was her impression that BHRT was protective against breast cancer but that is not the viewpoint of her PMD. She feels that she has been misled and is considering stopping the hormone program out of fear of breast cancer that was further stoked by her PMD.  

You reassure her that BHRT does not increase the risk of breast cancer, wherein it is probably protective against breast cancer. Although we cannot guarantee that a patient will not develop breast cancer, we can reassure patients that what we are prescribing does not increase the risk of breast cancer in any study in contrast with synthetic progestins that do increase the risk. Provide all the studies that have been reviewed in the webinars. She is content with your confidence and reassurance, particularly since you provided the scientific literature demonstrating the safety and efficacy of BHRT in comparison to SHRT. However, based on that which is written in the PDR, you document in her chart that she is advised of the risk of breast cancer based on that which is outlined in the PDR, but which is not EBM. It is your responsibility to warn the patient as well as document the warning in your written chart note, regardless of all the evidence to the contrary that BHRT does not increase the risk of breast cancer. Yes, we have to lie to the patient in order to conform to the standard of care. Despite what the PDR states, you provide evidence-based medical literature that refutes the risk that is stated in the PDR. The patient is pleased with the literature you provided to her, and she will pass these studies on to her PMD so that they can be better informed. She also ponders why her PMD gynecologist was not aware of all the EBM that you provided in addition to the safety and efficacy of BHRT.  

Respectfully,

Neal Rouzier  

References: 

1. Lieberman, A, Curtis, L. In Defense of Progesterone: A Review of the Literature. Alternative Therapies, Nov/Dec 2017, Vol. 23 No.6
2. Hipolito Rodrigues, M A, Gompel, A. Micronized Progesterone, Progestins, and Menopause Hormone Therapy. Women & Health. https://doi.org/10.1080/03630242.2020.1824956
3. Progesterone for Symptomatic Perimenopause Treatment- Progesterone Politics, Physiology and Potential for Perimenopause. Facts Views Vis Obgyn. 2011