Medical Mondays 2Dr. Patricia Yarberry Allen is a collaborative physician. Here, she asks Dr. Elizabeth Poynor, a gynecologic oncologist, to tackle a frequently asked question about what a patient should do when she needs to take a progestin, but her body can’t tolerate it.  

Dear Dr. Pat:

I am 60 years old and have been using low-dose hormone therapy (Menostar 0.014 estradiol) since I was 57 for osteoporosis treatment; I cannot take Actonel or Fosamax or other drugs like them by mouth because I have severe esophageal problems. I take calcium and Vitamin D and exercise, but it is not enough. I refused to take the IV drugs for osteoporosis because two of my friends used these medications and it caused them both to have awful symptoms for two years. I read about these drugs, and it seems that they stay in the body for a long time; this is unappealing to me. I am unable to tolerate progestins in any form. They all  make me feel like I am in a constant state of unmanageable PMS.

As a last resort my gynecologist did a biopsy of the lining of my uterus then inserted a Mirena IUD that delivers progesterone directly to the lining of the uterus in order to prevent the occurrence of endometrial cancer, which the estrogen just by itself can cause. I have no PMS symptoms from this progestin coated IUD!

 I know you can’t tell me as an individual what to do, but is this safe enough? Should I just have a hysterectomy and take away the risk? If I keep the Mirena in place, how often should it be removed, and how does the doctor monitor the lining of my uterus to see if the estrogen is causing cancer even with the progestin releasing IUD there? He said he would like to remove the IUD in two years and do a procedure in his office to look at the lining of the uterus and scrape away some of the cells for evaluation to make sure that this is safe.

I feel trapped because the estrogen, calcium, and Vitamin D, along with significant exercise, have increased my bone density over the last three years, but I know that as soon as I stop the estrogen, the bone density will drop again. What advice do you give patients with histories like mine? Is the FDA looking at the Mirena IUD to see if it can be used with estrogen as a way to prevent endometrial cancer?

 

Best,

Polly

 

Dr. Pat Responds:

Dear Polly:

The story you tell and the questions you have posed are heard often in gynecologists’ offices. These are, indeed, difficult issues to resolve. Preventing more bone loss is a serious reason to use hormone therapy when all other treatments have failed, and you are taking the lowest systemic dose of hormone therapy– 0.14mcg of estradiol–that has been demonstrated to decrease bone loss. But the problem you are facing is how to avoid the potentially serious result of unopposed estrogen therapy without a hysterectomy as your only certain answer.

The use of systemic estrogen alone when a patient still had her uterus was clearly shown to be a bad idea in the late seventies, when women developed a significant increase in endometrial cancer as a result of this treatment. This led to research that demonstrated that some form of progestin, given in a cyclic or daily regimen, would generally prevent endometrial cancer caused by systemic hormone therapy.

But, we do have patients who simply cannot function with systemic progestin or progesterone via a patch, injection, pill, or vaginal suppository. Now we have another progestin delivery system that is often tolerated by patients who can not use the other forms. The Mirena IUD (intrauterine device) releases  progestin to the endometrium to counteract the stimulation of growth of endometrial tissue caused by systemic estrogen. Some of that progestin is absorbed systemically, but little enough in your case to cause the symptoms you had with other forms of progestin therapy.

At the present time the use of the Mirena IUD to deliver a  progestin as part of estrogen/progestin hormone therapy is not considered the “standard of care.” But we are aware of women like you who need doctors on their medical team who will think outside the box with patients who will be vigilant in their follow-up.

There are no “absolutely certain” answers to your important questions, but I have asked Dr. Elizabeth Poynor, a WVFC board member and gynecologic oncologist, to let you know what we do know and what is on the horizon in this important field of post -menopausal hormone therapy.

 

Best,

Dr.  Pat

 

Dr. Poynor Responds:

The Menostar estrogen patch is considered an “ultra-low- dose” form of transdermal estrogen, which is FDA approved for the prevention of osteoporosis in post-menopausal women who are at elevated risk for low bone mass. After menopause a woman’s estrogen level precipitously drops, leading to increased bone resorbtion and increased risk of “thin bones.” This in turn results in an increased risk of hip and vertebral fractures. In a study of post-menopausal women, Menostar was shown to increase bone mass in the hip and lumbar spine, through suppression of bone turnover. Due to the risks of breast cancer, stroke, and blood clots, non-estrogen-containing treatments for osteoporosis prevention are generally considered as front-line treatment. However, some women will be unable to tolerate these therapies, and the ultra-low-dose estrogen patch may be used. These patches are generally not used for women who have a history of breast cancer, abnormal vaginal bleeding, or history of blood clots.

Whenever an estrogen is prescribed, a second type of hormone called a progestin is generally also prescribed for the woman who has a uterus present. When progestins are not used with so-called “unopposed estrogen” the risk of cancer of the lining of the uterus is significantly elevated. This risk elevation is dependent on the dose of the estrogen used and the duration of use. Women who use unopposed estrogen for less than one year have little risk of cancer;  however the risk increases 15-fold to 24-fold after 5 to 10 years of use. Standard, well-studied ways to protect the uterus  include: the use of medroxyprogesterone acetate (MPA–also known as Provera) either daily at a low dose (2.5 to 5mg) or cyclical for 10 to 12 days each month (10mg).

Other regimens which have been studied include quarterly (every 3 months) usage of progestins. Newer progesterone preparations have also been studied, although less rigorously than MPA; they include oral micronized progesterone (Prometrium) and vaginal progesterone. Some women will be symptomatic on progestins, with feelings of “PMS” such as bloating and weight gain and may do better with a more localized delivery of the medications directly to the uterus.

The Mirena IUD is a intrauterine device which is FDA approved for pregnancy prevention and treatment of heavy periods. It contains the progestin called levonorgestrel, commonly used in oral contraceptives. For women who suffer from the side effects of progestins, the Mirena IUD may be an attractive way to prevent the precursors to endometrial cancer and endometrial cancers that unopposed estrogen can cause. There has only been one small study published on the effectiveness of this regimen. In a small group of 150 women, 101 underwent a biopsy of the uterus after 40 months of use of estrogen and a levonorgestrel containing IUD. None of these women had precursors to cancer, or cancer.

For any regimen that is not standard of care, more intensive surveillance should be undertaken in order to assure safety. In the case of using a Mirena IUD with estrogen to prevent endometrial cancers and its precursors, this may include intermittent trans-vaginal ultrasounds and/or endometrial biopsy. The Mirena IUD is generally considered effective for five years for pregnancy prevention. Your physician may consider removing the IUD at four years and changing it in order to assure that adequate amounts of progestin are being delivered to the uterus. With any hormone replacement therapy regimen, any abnormal bleeding should be evaluated with an endometrial biopsy and ultrasound.

On a positive note, some experts have questioned how much progestin is really needed with our newer ultra-low- dose estrogen replacement therapies. Most of the studies with unopposed estrogen have been done with much higher doses of estrogens. Remember that there is a correlation between dose of estrogen and duration used, with risk of endometrial cancer. Some professionals have even advocated for the use of progestins as infrequently as every 6 to 12 months with the ultra-low-dose patch.

The bottom line: the safety of the regimen is not well proven; however,  it is a reasonable one after standard therapies have been exhausted; it is also reasonable to undertake more intensive surveillance while using this approach. It may also be reasonable to review with your physician other types of hormonal regimens, such as the use of the selective estrogen receptor modulator Evista, which does not require a progestin to protect the uterus.

Best,

Dr. Elizabeth Poynor

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