Stanford Fertility and Reproductive Medicine Center  

Primary Ovarian Insufficiency: Frequently Asked Questions

Click on the question for the answer:

How would I know if I have Primary Ovarian Insufficiency?

Some women who have POI in the earlier stages will have no symptoms. They will still have very regular cycles and the diagnosis may only come to their doctor’s attention when a fertility evaluation reveals low egg supply on the basis of an elevated blood level of follicle stimulating hormone (FSH) on the third day of the menstrual cycle or a low number of antral follicles in the ovaries visible on pelvic ultrasound. Antral follicles are the small sacs of fluid the ovary that each contains a microscopic egg.

Common symptoms (not present for all women):

What are the different ways in which women may experience Primary Ovarian Insufficiency?

Dr. Lawrence Nelson at the National Institutes of Health has suggested that we consider POI as a continuum of disorders.

Women do not necessarily progress through these different conditions in a linear fashion. In other words, women may have biochemical POI (elevated blood FSH), then develop overt POI (irregular cycles) and then experience a return to regular cycles for a period of time.

Who should be screened for Primary Ovarian Insufficiency?

Early diagnosis is important. If diagnosis is delayed, women can experience a lot of frustration unnecessarily suffering from symptoms related that can be treated. In addition, if POI is diagnosed early, it may be possible for some women who desire conception to conceive with their own remaining eggs.

Screening is recommended for POI if you have any of the following:

At Stanford we perform routine screening for women of all ages who are experiencing infertility (even if another cause such as male factor is also suspected) because it is not uncommon for us to find POI even in young women who are seeking fertility care at our center.

Risk factors for POI:

What are the initial screening tests for POI?

One of the most commonly performed screening tests is a blood test for both follicle stimulating hormone (FSH) and estradiol obtained on the third day of a menstrual cycle. This test can be helpful, but it is important to emphasize that sometimes the test result is normal even if a woman has POI. Furthermore, if one test is abnormal, it is likely that there is a problem with POI even if repeat tests are in the normal range. In some cases, if a woman has not had a recent menstrual cycle, a blood sample may be obtained for FSH, estradiol, and luteinizing hormone (LH) even in the absence of a menstrual cycle. It is very important that your physician be experienced in diagnosing POI because interpretation of these results is not always straightforward.

A pelvic ultrasound for antral follicle count can be very helpful, but also only if done by an individual who is experienced with assessment of egg supply by ultrasound. The thickness of the uterine lining on pelvic ultrasound can give a clue as to whether you have been producing estrogen over the preceding weeks.

A blood test for anti-mullerian hormone (AMH) on any day of the cycle may at some point in the near future become a screening test for POI. This test would have the advantage of less cycle to cycle variability compared with day 3 FSH and estradiol. However, normal ranges for this test are still being established and it is not yet being performed as a routine screening test.

If I have been diagnosed with POI, what other tests may be recommended?

The particular tests that would be recommended will vary depending on your individual situation and your age. Additional testing can be important because POI can have health implications for your general health as well as for your fertility. Although it can be discouraging to have to think about dealing with these health issues, if you are proactive, you can continue to maintain excellent health even after a diagnosis of POI.

Women who experience POI at a young age or women who have a suspicious family history (such as mental retardation) should be offered a blood test to determine if they are a carrier for a Fragile X premutation. In general, if you are experiencing POI in your late 30s or if you have POI because much of your ovarian tissue needed to be surgically removed for a condition such as endometriosis, this test would not be considered to be necessary. If you are at risk for being a Fragile X premutation carrier, it is important that you know this information because if you conceive, you may be at risk for having a child with autism or mental retardation.

If you experience POI under the age of 30, we recommend a blood test for karyotype to look for a condition called Turner’s syndrome. Instead of having two X chromosomes, women with Turner’s syndrome have only one X chromosome. If Turner’s syndrome is diagnosed, other tests are recommended such as an echocardiogram to look for abnormalities of the aorta. Because POI also puts women at risk for other health conditions, additional screening tests may be recommended:

What are the risks and benefits of hormone therapy for women with POI?

Over the last several years, much attention has been rightfully paid to results from the Women’s Health Initiative, a study of hormone therapy for postmenopausal women, mostly in their 50s or older. The study concluded that while hormone therapy protected against bone loss, it slightly increased the risk of developing breast cancer and heart disease. However, before these findings are applied to your decision-making about hormone therapy, it is very important to point out that the women in this study who took hormone therapy were very different from women who experience POI. For women who experience POI, the ovaries “should” have continued to make the hormones estrogen and progesterone for many more years, as the natural age of menopause is typically around 51. Hormone therapy for women who experience POI is true “replacement” for what the ovaries “should” be making while a woman is in her 30s and 40s. In contrast, women who participated in the Women’s Health Initiative were taking hormone therapy past the time that nature intended for the ovaries to be making hormones. They were in effect extending their lifetime exposure to hormones beyond what nature intended.

Unfortunately, at this time, there are no long-term data from large trials to guide women regarding the risks and benefits of taking hormone therapy when the ovaries stop producing hormones before age 40. It is very likely that hormone therapy will protect against osteoporosis. It is also clear that hormone therapy will reduce hot flashes and treat vaginal symptoms such as dryness. What is less clear is what the risks and benefits of hormone therapy are with respect to development of heart disease and breast cancer.

What options may be recommended if I wish to take hormone therapy for POI?

Although there are not definitive data to strongly justify any particular recommendation, in general it is suggested that women with POI who wish to take hormones choose a form that will best reproduce the way that the hormones would have been made by the ovaries if they had not stopped functioning. Estradiol and progesterone are the hormones naturally made by the ovary, and a case can be made for taking these hormones rather than synthetic forms such as ethinyl estradiol or norethindrone.

Estradiol is typically administered on a daily basis, as it is made by the ovary each day. A transdermal form of estradiol (patch or topical form) mimics the way the hormone would enter the bloodstream from the ovary better than oral (by mouth). The dose of estradiol for relief of symptoms in women with POI is often higher than the dose required for relief of symptoms for older menopausal women. Oral estradiol could also be considered if a woman prefers.

Progesterone is typically made by the ovary for only half of the cycle, and therefore if the goal is to reproduce what the ovary would normally do, taking progesterone for 12-14 days per month is commonly used. Progesterone is not well absorbed through the skin, and currently an oral form is recommended. Alternatives, such as an intrauterine or vaginal form, can be discussed with your doctor.

If hormones are administered in this fashion, monthly cycles will return. Side effects are often similar to what would occur with normal monthly cycles (e.g. pre-menstrual breast tenderness, bloating, and mood changes). For this reason, some women decide to take estradiol and progesterone daily to reduce the chance that menstrual-like bleeding will occur. This approach is acceptable, but is not mimicking natural ovarian steroid hormone production.

Some women with POI have been prescribed oral contraceptive pills. While this is not “wrong,” oral contraceptive pills are not physiologic (i.e. they are not mimicking what the ovary would naturally do). Oral contraceptive pills contain synthetic forms of estrogen and progesterone and also contain much higher levels of hormones than the ovary would naturally make. Women who still desire to keep open the possibility of spontaneous conception may prefer the option of the more physiologic way of taking hormone therapy (transdermal estradiol and oral progesterone), whereas other women may prefer the convenience of an oral contraceptive or a contraceptive patch.

If I prefer not to take hormones, what are my other options for addressing the symptoms I am having?

Non-hormonal alternatives for treatment of hot flashes are in general not as effective as hormone therapy, but may be adequate and acceptable for some women. These include venlafaxine, dressing in layers, exercise, and yoga. The literature is mixed regarding the effectiveness of black cohosh and red clover.

For vaginal dryness, some women find relief with the use of over-the-counter vaginal moisturizers. Other women may choose to take very low doses of estradiol (with very minimal absorption into the bloodstream). Vaginal lubricants can be used for intercourse.

Bone loss may be slowed by adequate calcium and vitamin D intake. Medications such as bisphosphonates are an option if childbearing is complete, but may not be optimal for women who wish to bear children in the future (with their own eggs or with donor eggs). Bisphosphonates stay in the bone, but can leach out gradually and theoretically enter the skeleton of a developing fetus, an effect with unknown safety.

What are my chances of conceiving if I have been diagnosed with POI?

The chance of conceiving with your own eggs depends on your age and the stage at which the drop in egg supply has been detected. If you were born without functioning ovaries and without eggs (a condition sometimes known as gonadal dysgenesis), then spontaneous conception will not be possible. On the other hand, spontaneous conceptions have occurred for women who have been formally diagnosed as being menopausal. This is true because even when the egg supply becomes very low and menses have not occurred for 6 months or more, an egg may still release and pregnancy may still occur. The chance of conception will drop with length of time since diagnosis. The timing of the egg release is unpredictable.

Unfortunately, fertility medications (tablets such as clomiphene or injections of gonadotropins) have not been shown to be helpful in promoting the release of an egg in most cases once a woman’s own FSH level has become very high.

In some situations, women have been told that they have “diminished ovarian reserve” rather than “premature ovarian failure.” In this situation, conception may very well still be possible, particularly if you are young. The likelihood of conception will vary depending on the severity of the drop in egg supply. It is a good idea to discuss your own particular situation with a doctor who is very familiar with POI in order to get an accurate picture of how likely it is that conception will be possible with your own eggs.

Women with even the most severe forms of POI can conceive and carry a child with the use of donor eggs. Although some people may prefer to choose adoption rather than egg donation, many people do choose egg donation as a way of building their family. With egg donation, a donor (usually anonymous, but sometimes known to the intended parents) will have eggs retrieved. These eggs will be fertilized with sperm from the intended father or from a sperm donor as appropriate. Hormones (estrogen and progesterone) are taken by the intended mother to prepare her uterine lining. One or two embryos are then transferred into the uterus of the intended mother. Hormone support is needed for the first trimester of pregnancy. Beyond that time, the placenta makes all the hormone that the pregnancy needs to continue. Delivery occurs just as if the pregnancy had occurred spontaneously. The mother can choose to breast-feed the child, also just as if the pregnancy had occurred spontaneously.

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