Last night the Portland OB/GYN Society, of which I am the current president, had the honor of hosting Dr Philip Sarrel to speak on the important topic of replacing estrogen in women who have experienced surgical menopause at an early age. His talk was fantastic, and illustrated the extreme importance of replacing estrogen in any woman who has experienced an unnatural loss of estrogen early in her life, and the ongoing benefit of estrogen replacement after menopause as well. I encourage you to review this video, which describes the findings of his research and his point of view, which I entirely agree with.
What was truly striking to me was the number of women who have had their ovaries removed at an early age. It saddens me, as I know that in many cases this is because of pelvic pain and endometriosis. While oophorectomy often does improve and in some cases even eliminate endometriosis pain, with proper resection of the the disease we can often achieve substantial and even complete pain relief while preserving ovarian function.
This is definitely worth a watch.
This week a study was published in JAMA Psychology drawing a connection between the use of birth control pills and depression. This was picked up in the popular press, and briefly we were hearing about it in the news and radio. I first heard about on my way to work listening to NPR. The message I got was that a study was just published that showed a link between the use of birth control pills and the development of new depression.
Today I read the actual paper that led to this media frenzy, and not surprisingly the media got it at least partially wrong.
Skovlund et al reported the following
“A total of 1 061 997 women (mean [SD] age, 24.4 [0.001] years; mean [SD] follow-up, 6.4 [0.004] years) were included in the analysis. Compared with nonusers, users of combined oral contraceptives had an RR of first use of an antidepressant of 1.23 (95% CI, 1.22-1.25). Users of progestogen-only pills had an RR for first use of an antidepressant of 1.34 (95% CI, 1.27-1.40); users of a patch (norgestrolmin), 2.0 (95% CI, 1.76-2.18); users of a vaginal ring (etonogestrel), 1.6 (95% CI, 1.55-1.69); and users of a levonorgestrel intrauterine system, 1.4 (95% CI, 1.31-1.42). For depression diagnoses, similar or slightly lower estimates were found. The relative risks generally decreased with increasing age. Adolescents (age range, 15-19 years) using combined oral contraceptives had an RR of a first use of an antidepressant of 1.8 (95% CI, 1.75-1.84) and those using progestin-only pills, 2.2 (95% CI, 1.99-2.52). Six months after starting use of hormonal contraceptives, the RR of antidepressant use peaked at 1.4 (95% CI, 1.34-1.46). When the reference group was changed to those who never used hormonal contraception, the RR estimates for users of combined oral contraceptives increased to 1.7 (95% CI, 1.66-1.71).”
In summary, women who used birth control pills were more likely to also use antidepressants. They concluded that women who use birth control use antidepressants more often, and thus they may be more likely to be depressed.
Here’s what I think about this.
When I talk to my patients, one of the greatest concerns I hear is regarding the fear that they might get a cancer at some point in their life. It is a very reasonable fear, as cancers of the female reproductive tract and breasts are not as rare as we might like. Perhaps educated by Angelina Jolie’s announcement of her BRCA mutation in 2013, many women now ask me about BRCA testing. In the past I referred to genetic counseling for this, but more recently I have become more educated on exactly who qualifies for testing, and send quite a few BRCA tests out of my office myself.
Across the board, somewhere between 1 in 8 and 1 in 10 women will get breast cancer over the course of their life, if they live to an age of 85 years old. Fortunately cure rates are high because we have many screening methodologies that are quite effective at finding it before it has spread widely, allowing for relatively straightforward treatments that are usually curative. These screenings include typical mammography, as well as high risk screening methodologies like breast MRI.
Ovarian cancer is far less common than breast cancer , affecting about 1 out of every 100 women, though it is also far more deadly. While breast cancer is usually caught early enough to be cured, ovarian cancer is usually found when it is already at an advanced stage, and even with treatment significantly shortens the life of women affected by it. We have investigated various strategies to screen for ovarian cacer, including ultrasounds and blood analyte testing (ie CA125), but to date no screening methodology has been shown to be truly useful in detecting the disease early, and unfortunately most women diagnosed eventually die from complications of the disease.
It is my impression that physician are very good at screening for breast cancer, and aware of women at high risk for ovarian cancer. This is a good thing. What we are not great at is identifying women who are at the highest risk of developing the disease : those that have heritable mutations such as BRCA mutation.
The most common heritable mutation for breast and ovarian cancer is BRCA 1 and 2 mutations. BRCA 1 is present in 2-3% of the general population, in 8% of women of Ashkenazi Jewish descent, and in 4% of Hispanic women. BRCA 2 is present in 2% of the general popuation, and in 1% of women of Ashkenazi Jewish descent, and in 3% of the African American population.
If a woman has a BRCA 1 mutation she is has a 60% chance of developing breast cancer by age 70, and a 50% chance of developing ovarian cancer.
If a woman has a BRCA 2 mutation, she has a 50 to 85% chance of developing breast cancer, and an approximately 30% chance of developing ovarian cancer.
Women that have these mutations can dramatically reduce their likelihood of dying from these cancers by doing advanced screening, and in many cases can consider removal of the potentially cancerous organs once they have completed childbearing (something brought into the mainstream awareness by Angelina Jolie a few years ago, who had a prophylactic mastectomy and oophorectomy for this reason.)
So given this important information, why are physicians not very active in ordering these tests?
The biggest reasons are two fold: 1) the tests are pretty expensive, with list prices between 2 and 4 thousand dollars depending on the lab and 2) the criteria under which these tests will be paid by insurance have been shifting in the last few years, and it has been hard to tell who will have their tests paid for and who will not. It is not worthwhile (or cost effective) to screen every woman for BRCA, but for women of high risk is is not only useful but also cost effective. But just how much risk is enough, and how do we quantify this and understand who will be covered for testing and who won’t? It is this question that keeps many qualifying women from getting screened in many physician’s offices today.
Fortunately, these issues have been greatly simplified in the last two years.
In general, BRCA testing will be covered by insurance for women who meet NCCN (National Comprehensive Cancer Network) guidelines for testing, which include:
1) women who have a direct relative positive for a BRCA mutation
2) women who have breast cancer at an age less than 50
3) women who develop triple negative breast cancer at an age less than 60 (i.e. negative progesterone receptor, negative estrogen receptor, HER2 receptor negative)
4) women who have had two different breast cancers
5) women who have a first degree (ie mother / sister) who had ovarian cancer _or_ who have a second degree relative (ie grandmother / aunt ) with ovarian cancer.
6) women who have two first degree relatives with breast cancer at any age
7) women who have one relative who had breast cancer at an age less than 50
Women with family histories of pancreatic cancer may also qualify, as this disease is also associated with BRCA mutation in some cases.
For women that meet these guidelines, testing should be largely covered by insurance, and in most cases are paid entirely by insurance. One strategy for appopriate testing is to routinely refer to genetic counseling, which if easily available will lead to the patient getting excellent information and counseling prior to having a test run, if appropriate. This strategy works great where there is readily available appointments, and with patients that are likely to follow a doctor’s recommendation to go to such a visit. There is, however, a subset of patients that will for whatever not reason not follow a recommendation to go to a genetic counselor. I think in many cases the concern for a heritable cancer is something that doesn’t directly influence a patient’s life, and they put addressing in on the back burner. As such, direct testing may lead to a greater likelihood of actually testing appropriate women, and is reasonable to consider in some practices. In the end, I think the most important thing is that physicians keeps the issue in front-of-mind, and appropriately manage patients with a strategy that makes sense for each individual patient.
In the last few years, I have begun to test far more women than I used to. While I have only found a single woman who actually had a BRCA mutation, I have consistently found that women who are tested and are found to be negative really appreciate having had the opportunity to be tested, and feel great reassurance that they do not have the mutation, which is of value in itself.
So if you are a physician and are not considering testing appropriate patients for BRCA, make it a more prominent part of your practice, whether that be through direct testing or routine referral to genetic counseling. If you are a woman who has a concern about your family history of breast or ovarian cancer, please ask your doctor if its appropriate for you to be tested, either directly or through referral to a genetic counselor. Because while screening the general population for the actual cancer is important, finding the women who are at the highest risk is also an important part of care.
Dr. Fogelson practices gynecologic surgery and general gynecology at Pearl Women’s Center in Portland, OR. He can be reached at (503) 771-1183, or http://www.pearlwomenscenter.com./
Not surprisingly, this post has gotten a lot of interest, mostly negatively from the genetic counseling world. The gist is that that genetic counselors think it a terrible idea for a non-genetic counselor to order these types of tests without referring to them first, which I did suggest in the original text.
In many ways, I agree with them. They have years of training and a deeper understanding of each potential mutation than most physicians have (absent physicians with genetics fellowships). They also have more time to talk to patients about these issues, and thus can be more thorough in their counseling. As such, the optimal course for patients who are considering BRCA testing, or any other genetic counseling, is to see a genetic counselor first. Some insurers (Aetna I’m looking at you) even require it.
We must also recognize, though, that these genetic counselors see the world through a different lens than a physician that refers to them. They see patients that come to see them and do a great job with them. What they don’t see are the women who had discussions with their doctors about seeing genetic counselors, but that never actually came to see them.
In most cases, a concern for a heritable cancer syndrome develops because of a routine history with a thoughtful physician. It is only the minority where a patient actually comes in with the expressed concern about a heritable cancer syndrome. So in most cases, it is the physician who is bringing up the issue and saying “hey we should consider this issue”. Now this consideration can be referral to a genetic counselor, or it may be considering if direct testing is appropriate. What I know from experience, is that if I pass it off to a genetic counselor, a substantial number of patients are going to take my advice to go se them and not act on it. After all, a genetic predisposition isn’t a sickness that a patient can feel. If somebody has chest pain and I refer them to a cardiologist, they are going to go. But if they have a completely unseen and unfelt predisposition to some future disease, maybe they won’t. In fact, definitely some won’t. So the hard line everybody has to see a genetic counselor prior to testing is missing this point, in my opinion. I think that it is entirely reasonable to ask a patient if they would like to see (or even recommend that they see) a genetic counselor, and also entirely reasonable that some patients may be tested directly. After all, individualized care is what we do.
In the end, I think this question is a bit of a distraction, and not really the point of my article anyway. What is important is that physicians think about this issue more. Many physicians don’t think about it much at all, and may neither refer to a genetic counselor nor order appropriate testing. And that is something worth trying to change.
In light of this issue, I have edited the original article a bit, as I do think it was a little too much against sending to genetic counseling, which was perhaps misguided.
Dr Nicholas Fogelson of Pearl Women’s Center in Portland, OR demonstrates a technique for temporary ovarian suspension. This technique is useful for lifting the ovaries off the pelvic sidewall, exposing the area for treatment of endometriosis or other pathology.
I recently was looking into whether or not you should place a paracervical block before placing an intrauterine device, after a particular patient had a difficult time with a placement. Over my career, I generally haven’t done so, as the vast majority of patients don’t seem to have a significant amount of pain, and the literature I have read has not been very supportive of the practice.
Today I looked at the literature again, and was a little irritated at what I found. One particular study was Mody et al, which concluded “Compared with no anesthetic, a 1% lidocaine paracervical block did not result in a statistically significant decrease in perceived pain with IUD insertion.”
So clearly most would read this and say that it doesn’t matter if you put in a paracervical block or not.
But’s here’s the kicker; the summary of their data is the following: ” Twenty-six women received the paracervical block before IUD insertion, and 24 received no local anesthesia. Groups were similar in age, parity, ethnicity, education and complications. Women who received the paracervical block reported a median VAS score of 24.0 mm with IUD insertion, and women who did not receive local anesthetic reported a median VAS score of 62.0 mm with IUD insertion; p=.09.”
So patients who got a block had pain of 2 on a scale of 2 to 10, and patinets who did not have a block had pain of 6 on the same scale. So did the paracervical block really not work?
I would say it did. What didn’t work was the study, or at least most likely so. The p value, or likelihood that the outcome was do to statistical chance alone, was 0.09. In translation, there was a 9% chance that the difference between the groups was due to chance alone, and a 91% chance that it was due to an actual effect of the paracervical block. Since we arbitrarily say that a p of 0.05 is statistically significant, the authors say that the study was negative.
But isn’t this quite misleading? It is 10 to 1 likely that the paracervical block actually made the procedure less painful, and we just didn’t reach a p of < 0.05 because there weren’t enough patients in the study to adequately separate the groups mathematically (lack of power).
P values are important, but we can’t consider them to be everything. Statistical significance is a continuous variable, not a nominal one. If we say that p=0.049 means that the study shows a difference and p=0.051 means there was no difference, we are just being foolish, and in the end quite ignorant of the actual mathematics that goes into how the p value was created.
Here’s how I would like to see such a study concluded : “Compared with no anesthetic, a 1% lidocaine paracervical block showed a strong trend towards decreasing pain with IUD insertion, that did not reach statistical significance. Further study with a greater number of patients is warranted.”
If you read their conclusion, you would probably take from that that paracervical blocks don’t work. But if you read mine, you take a different message, which is actually supported by the data, which would be “It is very likely that paracervical blocks decrease pain with IUD insertion”, which of course makes sense
Mody SK; Kiley J; Rademaker A; Gawron L; Stika C; Hammon C. Pain control for intrauterine device insertion: a randomized trial of 1% lidocaine paracervical block. Contraception. 2012; 86(6): 704-9.
As many of my readers know, I spend a fair amount of time online. I love interacting with other docs that do what I do, and even more so, I love interacting with women that have the conditions that I treat. Even though I have left academics, I am a teacher at heart, and enjoy the opportunity to pass on what I have learned when I can.
One of the biggest questions I see is about how endometriosis care is paid for.
Unlike typical care, many endometriosis physicians are not under contract with insurers for care. This creates a whole different system for payment of medical care that is confusing to many patients – so let me explain it here. Read more…
Recently I read an article by Lena Dunham, describing her life with endometriosis, treatment she has undergone, and how her life has been since. Its a very poignant article about a successful woman who has been held back by her condition, yet also a story of incredible perseverance despite tremendous barriers. Ms Dunham is a successful actress, producer, writer, and director, having created multiple films and the wildly successful (and awesome!) HBO series Girls, both as writer/director/producer and as principal actress. She is also a woman who did these things despite tremendous pain from endometriosis.