Academic OB/GYN

This month’s Grey Journal feels a little light on substance, but one article I liked was an article looking at a new protocol for use of methotrexate for treatment of ectopics(1).  This protocol looked at giving a second dose of MTX if the day 7 HCG is not 50% lower than the Day 1 HCG, without checking a day 4.  This is opposed to a typical single dose protocol, checking a day 4 and repeating MTX if the day 7 is not 15% lower than the day 4.

This study was based on data abstraction from 187 patients who were treated with single dose MTX for ectopic pregnancies, with demographics and HCG levels recorded over time.   Based on these data, a comparison was made between a Day 1,4,7 strategy and a Day 1,7 strategy.  Here’s what they found.

A Day 1,7 strategy has a very high sensitivity for picking up women who need another dose of MTX to successfully end an ectopic pregnancy, but a much lower specificity.  This means that with a Day 1,7 strategy many more women will get treated with a second dose of MTX than with a Day 1,4,7 strategy.  However, in tradeoff they will not need to get a day 4 blood draw.  Depending on Beta HCG levels, anywhere from 2 to 10 additional women will get a second MTX dose per Day 4 blood draw avoided with this strategy.

So here’s a few thoughts on this:

1) This strategy leads to a lot more methotrexate use, in order to avoid a blood draw.  From a cost point of view this could be a problem. Dr Thurman points out that MTX is inexpensive, but in many hospitals it is delivered as a chemotherapy agent.  Even if it is  regular injection, it usually isn’t available in the MD office and hospital nursing charges are high.  Actual cost of drug is low, but delivery of drug can be expensive.

2) Some people think we should be doing 2 dose MTX for everybody anyway.  Failure rates for single dose MTX are around 10% in a mixed population (2), though a mandatory 2-dose regimen hasn’t done much better in trials(3).   This regimen would be a middle ground between a 1 dose and mandatory 2 dose regimen.

As this is just pilot data, it will be interesting to see this against a 1,4,7 regimen in a randomized trial.  I know several of the investigators, and suspect that they will be doing this in the future.  I look forward to those results.   For now I will still use a 1,4,7 regiment, as to me a day 4 lab draw is not as big a deal as a second dose of MTX.  But that being said, if a patient really hated getting blood drawn, this might be a better option for them.   Then again if they hate blood draws much, maybe a laparoscopy would be better!

Source:

Thurman AR, Cornelius M, Korte J, Fylstra D. An alternative monitoring protocol for single-dose methotrexate therapy in ectopic pregnancy. Am J Obset Gynecol 2010; 202:139.e-16

Lipscomb GH, Bran D, McCord ML, Portera C, Ling FW. An analysis of 315 ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 1998;178:1354-1358

Barnhart K, Hummel AC, Sammel MD, Menon S, Jain J, Chakhtoura N
Use of “2-dose” regimen of methotrexate to treat ectopic pregnancy.
Fertil Steril. 2007 Feb;87(2):250-6. Epub 2006 Nov 13.

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When Ortho Evra, the contraceptive patch came on the market, physicians were happy that women had a new and novel contraceptive method that significantly expanded options over what was already available.  Since that time, hundreds of thousands of women worldwide have safely used Ortho Evra for birth control.

As the transdermal patch was a new delivery method for birth control, several new pharmacokinetic studies were done postmarketing, in addition to those done prior to FDA approval.  One of these studies demonstrated that patients using Ortho Evra had on average 60% higher estrogen blood levels than patients on oral contraceptives, despite lower peak levels (1).  Given that estrogen somewhat increases the risk of venous thromboembolism(VTE), this data raised the concern that Ortho Evra might confer a greater attributable risk than traditional oral contraceptives.

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The new USPTF guidelines for breast cancer screening have been a super hot topic for the last week.  We started out with outrage, moved to outrage at the outrage, and are finally settling into a state of reasonable interpretation.   The growing consensus (that I’ve seen) is that the USPTF guidelines are not so far off, but their wording could have been much better.   It is true that mammograms before the age of 50 have a low positive predictive value, and thusly a high false positive rate.  It is also true, based on the USPTF data, that for every 1000 women screened annually between 40 and 50 years of age, over 50% of them will need additional imaging at one point, 20% will get a breast biopsy, and only 1-2 breast cancer deaths will be prevented.  Based on this, it is clearly worth discussing whether patients 40-50 should be getting mammograms.

But the world, at first, didn’t want to discuss it.   We immediately attacked the USPTF, even accusing them of somehow being in league with new health care reform policies meant to reduce costs, at the known expense of women’s lives.  Even Sanjay Gupta went attack dog against one of the USPTF members live on CNN.  That was the most surprising thing to me.

But now people are starting to come around, and they are coming around pretty much to where I started.

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Tranexamic acid was recently approved by the FDA for treatment of fibroid related mennoraghia, under the trade name Lysteda.  Being ignorant of this drug, I wanted to do a  little research.  Being a blogger, I want to share this research.

Apparently, this drug has been available in Europe for quite a long time, and there is substantial evidence of its efficacy and safety for treatment of a wide variety of bleeding issues, both gynecologic and otherwise.  Tranexamic acid (Wiki, WA) is in class of drugs called antifibrinolytics.   It is related to the drug Amicar (ε-aminocaproic acid) which is used in the US most notably after dental procedures as a mouthwash in patients with bleeding disorders.  These drugs function by blockade of lysine binding sites on plasminogen, thus blocking degradation of plasminogen into plasmin (sort of an anti-tPA).  Through this mechanism it stabilizes clots and prevents clot breakdown, thus augmenting the clotting system and decreasing bleeding.

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