February 22, 2020 at 08:00PM by CWC
If you’ve ever gone to a fertility doc for testing, you’ve likely had a blood taken to measure your levels of anti-Müllerian hormone (AMH) to as a relatively accurate measure of your ovarian reserve (i.e., roughly how many eggs you have left). While AMH is currently used only to help manage infertility, however, some doctors would like to use levels to more accurately predict when a woman will go through menopause—a big deal, they say, since current tests aren’t really very helpful until a woman’s periods are already over.
In a study published last month, researchers measured levels of AMH and FSH (follicle-stimulating hormone; elevated levels of which are used to check for menopause) in 1537 premenopausal women in their mid- to late-40s regularly until the women had gone through menopause. They used a more sensitive AMH test than what’s been tested to-date and were able to start closing in on an AMH level that seemed to correspond with a likelihood of having a final menstrual cycle (and thus marking the official menopause period).
The test used in the study (Menocheck or the Ansh PicoAMH assay) was the first AMH menopause test approved by the Food & Drug Administration (FDA) in 2018 to predict menopause in conjunction with other tests and assessments. Study author Nanette Santoro, MD, the chair of obstetrics and gynecology at the University of Colorado School of Medicine (who became a consultant for the maker of the test, Ansh Laboratories, since the research was published), notes that the test is about 10 times more sensitive than previous tests. The study used information from the Study of Women’s Health Across the Nation (SWAN), a high-quality, long-term study that’s produced a wealth of information to help doctors define and manage menopause, notes Julian Peskin, MD, an OB/GYN at Cleveland Clinic who specializes in menopause.
So what were the results of the menopause testing study? According to the study, someone with an AMH level lower than 10 pg/ml had a 51 to 79 percent likelihood to experience their last menstrual cycle within in the next 12 months (depending on their age), while a person with AMH levels higher than 100 pg/ml had a 90 to 97 percent likelihood of not experiencing their very last menstrual cycle within the next 12 months.
Most people with uteruses go through menopause around the age of 51. Knowing that, what difference does a test that can narrow the window by a couple years really make? Potentially a lot, since menopause and all its symptoms can be pretty terrible for some people. But experts say we’re still a ways away from being able to give an accurate prediction of the onset of menopause.
The appeal of an accurate blood test for menopause
Currently, doctors only run FSH and estrogen tests for menopause on request. Both of these hormones are less accurate, indirect indicators of ovarian function than AMH, since they’re produced by the pituitary gland and not the ovaries. “It’s a bad marker of menopause. It doesn’t tell us exactly what the ovary is doing,” says Dr. Peskin. Plus, since levels of these hormones can vary wildly throughout perimenopause (the years leading up to menopause) and even a single menstrual cycle.
Meanwhile, experts have a lot of faith in the potential for using AMH to predict menopause, because it more directly relates to ovarian function. At birth, people with uteruses are born with all the eggs they’ll ever have—roughly a million in all. Egg quantity and quality declines with age. By puberty, about a third of a person’s eggs remain, and the follicles in their ovaries begin producing AMH. Levels of this hormone max out when people with uteruses are about 25 and gradually decline with age, until they’re virtually undetectable at menopause. Generally speaking, the more eggs a person has, the higher their AMH levels. And once a person no longer has eggs, they stop having a menstrual cycle—which, hello, menopause.
High AMH levels can help doctors rule out that menopause is coming within the next four to five years, regardless of a woman’s age, explains Dr. Santoro. And having more accurate AMH readings can be helpful to know when menopause will arrive within the next year, as long as a woman is at least 50. “It provides very high assurance that menopause will occur within the coming six to 12 months,” she says.
“I do think it can be very valuable tool in counseling women. If a woman is in her early 40s and already close to menopausal levels, we can counsel her that she’ll experience it earlier.” —Mindy Christianson, MD
Although predicting menopause wouldn’t change how doctors treat women in the short term, knowledge is power. “On a daily basis, women come in at 47, 48, or 49 with irregular periods, night sweats, and vaginal dryness and want to know when it will all come to an end. Our arsenal is very limited with FSH and estradiol,” says Dr. Peskin.
“I do think it can be very valuable tool in counseling women,” says Mindy Christianson, MD, a reproductive endocrinologist and the medical director of the Johns Hopkins Fertility Center.. “If a woman is in her early 40s and already close to menopausal levels, we can counsel her that she’ll experience it earlier.”
In the long term, better predicting a person’s age at menopause could help doctors take steps to manage conditions that affect postmenopausal people, like bone loss and heart disease, says Dr. Peskin. And since a person who has a period for more years may be slightly more likely to receive a breast cancer diagnosis, knowing that they’ll go through menopause later could help doctors take steps to reduce risk earlier, he adds.
Many pre-menopausal women with irregular patients also ask if they can stop using contraception; because they could still be ovulating, “the standard response is no,” says Dr. Peskin. Having a more accurate test could help doctors to better counsel patients on how much longer they’ll likely want to use birth control.
One in four women in their late 40s to 50s also experience fibroids that sometimes need to be surgically removed. Because estrogen feeds fibroids, the irregular bleeding they cause disappears after menopause. More accurate menopause testing could help doctors to counsel women when surgery is necessary, or when someone in their late 40s can take a wait-and-see approach with fibroids because it’ll all be over soon when they go through menopause. “It’s an excellent reason for testing,” Peskin says.
The current limitations of AMH for predicting menopause
AMH has a lot of potential for helping doctors pinpoint exactly when a person could expect to go through menopause. (Emphasis on potential.) But past research using less sensitive AMH tests to predict menopause has been mixed. A 2016 study of 155 women that looked at various tests of ovarian reserve found that although AMH levels were the best predictors of menopause by age, they weren’t highly accurate in individual cases and couldn’t predict extremes (very early or late menopause). Another 2019 study that measured AMH levels in 2434 premenopausal women every five years for 20 years found that looking at the rate of AMH decline over time couldn’t predict menopause or early menopause.
AMH measurements are also an imperfect indicator. “It may be one value at one point, and six months later it could be higher, which you wouldn’t expect,” says Dr. Christianson. “I have checked AMH levels to see if a woman is menopausal for various reasons, and even when [AMH is] at its lowest value, a woman can still have ovarian function.”
Some doctors are also concerned that AMH tests can be misused in trying to help people plan for future children. “AMH is one of a number of tools we use to understand what a woman’s ovaries can still do in the present, but AMH cannot tell you whether a woman can or will get pregnant,” says Norbert Gleicher, MD, the medical director and chief scientist at the Center for Human Reproduction—because there are so many other complex factors that can impact fertility.
About 10 percent of women have premature ovarian aging, notes Dr. Gleicher, meaning they go through menopause before the age of 40. If they want to start families, it’s important to try for kids earlier. But current AMH tests can’t predict when people with uteruses in their 20s and 30s will go through menopause—or even if they’ll go through it early, he adds. Doctors can combine AMH with a couple of other blood tests and answers to a few questions to determine if a person is at risk of premature ovarian aging, at which point they’ll recommend annual testing. “The only way to know is if you follow women for few years to see if staying on normal aging curve or if they deviate,” he says.
Dr. Christianson adds that there’s simply not enough data yet to nail down a bulletproof “normal” AMH level by age, since there can be significant variation from person to person in the years leading up to menopause. What’s more, she says, the various companies currently offering AMH tests often find different levels using the same sample.
“This is not a test that is necessary for many women, and the clinical context and appropriateness of the test need to considered before ordering it.” —Nanette Santoro, MD
All of these factors led the American College of Obstetricians and Gynecologists (ACOG) to issue a committee opinion in 2019 saying that while AMH is relatively reliable in measuring ovarian reserve, testing should currently only be used in women undergoing infertility treatments, not to predict menopause. The group notes note that studies don’t show that current AMH tests accurately predict a woman’s chances of getting pregnant, and that they aren’t sensitive, precise, or subject to international standards, making results variable and at times difficult to interpret. “It’s written so that OB/GYNs wouldn’t tell patients, ‘you have 10 years of fertility so there’s no rush,’” says Dr. Peskin.
“This is not a test that is necessary for many women, and the clinical context and appropriateness of the test need to considered before ordering it,” says Dr. Santoro, who authored the study published in January. “This evidence was not available to ACOG a year ago, and it is really the first set of evidence demonstrating the usefulness of AMH for prediction of the final menstrual period.” She adds that ACOG will want to see more studies before they recommend using AMH to predict menopause.
We’re still a ways off from AMH being the end-all, be-all for determining when exactly a person will go through menopause. But that could change in the near future, per Dr. Santoro’s points, as more scientists research and develop tools to help make interpreting that data more useful and accurate. And having that information in the right hands can be powerful—and empowering to patients. “Menopause can be disabling discouraging and significantly impact quality of life. It gives us some extra ammunition or to help patients with the transition,” says Dr. Peskin.