The Management of Chronic Gynecologic Conditions During COVID and Beyond - Episode 10

Risks/Benefits of Medical Treatment for HMB Associated With UF

March 15, 2021
Ayman Al-Hendy, MD, PhD

Linda Bradley, MD

Stacey Missmer, ScD

Eric Surrey, MD

Supported by: AbbVie

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Ayman Al-Hendy, MD, PhD, reviews the risks and benefits associated with the medical treatment options used to treat HMB from uterine fibroids.

Ayman Al-Hendy, MD, PhD: If we try to utilize the same approach for medical therapy, the risk/benefit for the various medical treatment options for management of heavy menstrual bleeding associated with fibroid. The list of medical treatments includes things like tranexamic acid, oral contraceptives, progestin, GnRH agonists, and then the more recent group, GnRH antagonists.

I would say, of course, we are very creative people in gynecology, and we always try to develop some medical treatment approach, even if the basic science kind of suggests going in a different direction. For example, with the oral contraceptive and the progestin, we talked earlier about endometriosis as being a progestin-resistant disease. So it would make sense to add more progestin. Fibroids actually are a progestin-hypersensitive lesion, and yet we’re actually using progestin and oral contraceptives. The reason this survived the test of time for a while is because of the good effect on the endometrium. Basically, it makes the endometrium quite atrophic, and the patient will enjoy I would say temporary improvement of their heavy menstrual bleeding, not because of the positive effect or the beneficial effect on the fibroid, just on the endometrium. As oral contraceptives, many people usually use it as first line for management of heavy menstrual bleeding with fibroids. There is limited data, definitely very limited long-term data. Usually it shows some benefit in about 40% of patients for 3 to 6 months. Again, long term they tend to fail. Progestin has a very similar result, and of course with the progestin, you get the breakthrough bleeding and the unpredictable irregular bleeding.

Tranexamic acid, and I know I might get in trouble with Linda on that one, I know she loves that one. I would say it’s a good option, but I want to say the studies that developed this really was mostly focusing on ovulatory, what we used to call dysfunctional uterine bleeding, although they did include also a limited cohort of fibroid patients. But it’s certainly an option, and I know in the right hands, it might give good results.

Then we go to the GnRH agonists, and it’s a very similar story to what we talked about a few minutes ago in endometriosis. It causes severe hyperestrogenic status, and of course the fibroid will shrink and suffer, and the patient will enjoy the improvement in their bleeding; however, at the cost of the severe, could be serious side effects such as irreversible bone loss if you use it beyond 6 months and hypo-estrogenic menopausal symptoms. Of course, then we improvise with the add-back therapy.

I’m really excited about the new group of compounds, the oral GnRH antagonists. These are non-peptides, so we can use them orally. They’re not going to be digested or destroyed in our GI tract, and that’s really very convenient for the patient. Of course, we know GnRH analogue are injectable, and also they have been developed with the right amount of combination of very little amount of add-back therapy. There are 3 members in that family, and all of them are using the same add-back regimen of 1 milligram of estradiol and half-milligram of norethindrone acetate. They are all being evaluated in very well done, very well designed, highly powered clinical trials, so we have reliable data that we can use to counsel our patients with good, long-term successful response. I’m very excited about that group, and I’m hoping that might change the paradigm to give our patients more non-invasive treatment options.

Of course, with the exception of the tranexamic acid are all of these are hormonal options. Obviously, they exploit what we know about fibroids are estrogen-progestin dependent. The disadvantage, of course, of all of these treatment options, they are fertility incompatible, or what I call fertility unfriendly. What I mean by that is, 1, you’re using any of these treatment options, whether the oral contraceptive, progestin, GnRH antagonist, or GnRH agonist, you cannot pursue pregnancy. If you are somebody who is young or mid-productive years, and you have fibroids, and you still want to start the family or complete your family and you’re suffering from symptoms related to fibroids, you have to pursue one of the other. If you want to control or improve your fibroid symptoms with these options, then you have to do this, and put your plans to pursue a pregnancy on hold for a certain amount of time, whether it’s 6 months, a year, etc. Then after you accomplish that, then you go and pursue pregnancy. Clearly, that is a challenge in the field, and it’s something I think begs for the need for non-hormonal treatment options for fibroids that could be fertility friendly so the patient can manage her symptoms or improve her symptoms while pursuing a pregnancy.

Transcript edited for clarity.

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