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Premature Ovarian Failure – What Do I Need to Know?

By Linda R. Nelson, MD, PhD
Published in Resolve for the journey and beyond, Summer 2012

Many women younger than 40 experience irregular menses (oligomenorrhea), and some women may even skip periods (amenorrhea) for months at a time. There can be many reasons for irregular or skipped menses in young women, but Premature Ovarian Failure (sometimes called primary ovarian insufficiency) is one of the less common causes.

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Premature Ovarian Failure (POF) affects 1 in 100 women younger than 40 years of age. This condition needs to be completely evaluated since there are often associated medical conditions that need to be treated. In addition, options for fertility may exist if a woman desires pregnancy.

Ovarian failure usually occurs at menopause when there are very few eggs and follicles left in the ovary. Estrogen levels decline due to the loss of the ovarian follicles that provide high levels of estrogen and progesterone during the menstrual cycle. The average age of menopause is 51 years of age and it is very common for women to have symptoms of estrogen loss and irregular cycles in their mid to late 40’s.

However, women with POF have symptoms of early menopause including hot flashes, sleep disturbances, vaginal dryness and painful intercourse along with a lack of regular menstrual cycles in their teens, 20’s or 30’s.

Making the Diagnosis

The first step in making the diagnosis is a blood test to check whether or not the ovary is producing estrogen and the whether the pituitary gland is producing the hormones FSH and LH that stimulate the ovarian follicles. If the pituitary hormones are elevated and the ovary is not producing estrogen, then the diagnosis of POF is made. A transvaginal ultrasound may also be done to evaluate the ovaries. In POF patients, the ovaries are usually small and there are few follicles seen.

Finding the Cause

In many cases, a cause for POF cannot be found. A history of chemotherapy or radiation treatment for a childhood illness is the most common cause of POF. There are autoimmune causes of POF. In these cases, the immune system attacks endocrine organs including the ovaries, thyroid and adrenal glands. Lab tests can detect some of the antibodies directed at these glands, but it is not possible to detect all the immune factors that may be important. Women thought to have an autoimmune factor will need to have their thyroid and adrenal gland checked regularly because failure of these glands can lead to serious or life-threatening medical conditions.

There are also genetic causes of POF. Evaluation of chromosomes is often the initial step. In rare cases, women may have Y chromosome material present, which can lead to tumors in the ovaries if they are not removed. More commonly, there is only one normal X chromosome instead of 2 and this is called Turner syndrome or monosomy X. Women with Turner Syndrome may also have heart, vascular or kidney problems that need to be investigated. Fragile X syndrome is an abnormal expression of a gene on the X chromosome that leads to mental retardation in boys when the defect is “fully expanded.” This genetic defect can also be present as a “premutation” in women with POF. There are other rare genetic defects that may also be diagnosed within families or as new mutations.

Lastly, there can be defects in the production or activity of pituitary and ovarian hormones. In these cases, follicles are present in the ovary but they cannot be stimulated to achieve a pregnancy.

POF Treatment Options

Loss of estrogen can lead to many symptoms (see above) that can be treated with estrogen therapy. There are also several medical conditions that may be prevented by restoring estrogen in young women. These include bone loss (osteopenia) and vaginal atrophy. The relationship of estrogen to heart disease in young women is still controversial, but a lack of estrogen leads to abnormal cholesterol and lipid levels that can be reversed by estrogen therapy. In women without any contraindications, estrogen treatment would be recommended for these symptoms and disorders until the age of natural menopause (around 50 years of age). The risks of hormone use are generally age-related, and your physician will evaluate whether there are any contraindications to taking estrogen and progesterone. If there are, other non-hormonal treatments can be tried, and a healthy diet and exercise are always recommended to prevent heart disease, osteoporosis and obesity.

Infertility results from the loss of healthy eggs and follicles. For young women with POF menstrual cycles can still occur even years after the diagnosis and 10% of women with POF will conceive on their own. This is likely due to ovulation of a healthy egg even after months of skipped menses. There have been attempts to treat women with ovulation induction agents or other medications to improve fertility, but there is a lack of clear evidence that these treatments work. Most women with POF will not get pregnant with their own eggs. However, it is possible to become pregnant and carry a baby using eggs from another woman with a donor egg in-vitro fertilization cycle.

Depression and anxiety are very common in women with POF. A therapist or mental health professional may be able to help with these problems. RESOLVE also provides in-person and on-line support groups that can be very helpful as well.

Linda R. Nelson, M.D., Ph.D. is a Professor at the University of Arizona College of Medicine, Phoenix and an OB/GYN at the Fertility Centers of Arizona. Dr. Nelson is Board Certified in Reproductive Endocrinology and Infertility and Obstetrics and Gynecology. Dr. Nelson specializes in all aspects of patient care including IVF, IUI, minimally invasive surgery and medical management of reproductive endocrine disorders. She has been recognized as a “Super Doctor” by Arizona magazine, and U.S. News and World Report named her one of the Nation’s Top Reproductive Endocrinologists in 2011.