Patient information: Early menopause (primary ovarian insufficiency) (Beyond the Basics)
- Lawrence M Nelson, MD
Lawrence M Nelson, MD
- National Institutes of Health
- Section Editors
- William F Crowley, Jr, MD
William F Crowley, Jr, MD
- Section Editor — Female Reproductive Endocrinology
- Daniel K. Podolsky Professor of Medicine
- Harvard Medical School
- Robert L Barbieri, MD
Robert L Barbieri, MD
- Editor-in-Chief — Obstetrics, Gynecology and Women's Health
- Section Editor — General Gynecology and Female Reproductive Endocrinology
- Kate Macy Ladd Professor of Obstetrics, Gynecology and Reproductive Biology
- Harvard Medical School
PRIMARY OVARIAN INSUFFICIENCY OVERVIEW
Primary ovarian insufficiency (POI) is a condition in which the ovaries stop functioning normally in women who are younger than 40 years. The condition used to be called “premature ovarian failure” and “premature menopause,” but these terms are misleading, because women with POI do not always stop menstruating (having periods), and their ovaries do not always completely shut down . That's important to keep in mind, because the diagnosis of POI does not always mean that pregnancy is impossible. What's more, the condition does not imply that a woman is aging prematurely. It simply means that her ovaries are faltering.
In women with POI, the ovaries:
●Stop releasing eggs, or release them only intermittently, and
●Stop producing the hormones estrogen, progesterone, and testosterone, or produce them only intermittently
Given these effects, POI makes pregnancy unlikely. Learning of this can be emotionally devastating to some women, especially if they have not had children or want more children. For them, the diagnosis squelches dreams of motherhood. If that is true for you, take some time to heal emotionally and to learn about your options.
Take time to honor your feelings of grief and loss. Being diagnosed with POI can be a life-changing experience . It is natural to feel down, but be mindful of depression. You may even want to seek out counseling or to participate in a professionally-monitored support group for women with POI. If you have a partner, remember that he or she may also be affected by your diagnosis, so it might be useful to find help in processing related emotions for the two of you.
PRIMARY OVARIAN INSUFFICIENCY CAUSES
In the vast majority of cases, healthcare providers do not know why primary ovarian insufficiency (POI) occurs. Some cases of the condition can be explained by genetic abnormalities, exposure to toxins, or autoimmune disorders, but most cases are “idiopathic,” meaning they have no known cause . Even so, it is important for women to be tested for the known causes of POI. Some of the known causes may be associated with other effects on your health or the health of your family members.
Genetic causes — Genetic causes of POI may be due to abnormal chromosomes or abnormal individual genes. Chromosomes are structures that house thousands of genes. Chromosomal abnormalities that lead to POI include:
●Turner syndrome – The sex of a person is determined by their complement of X and Y chromosomes. Women normally have two X chromosomes, while men have one X chromosome and one Y chromosome. In Turner syndrome, women have only one X chromosome; the other one is missing. The lack of a second X chromosome (Turner syndrome) is the most common chromosomal defect in humans. It causes abnormalities throughout the reproductive system and can cause POI. Missing just a portion of one X chromosome (a critical portion) can also cause POI.
●Fragile X syndrome – Fragile X syndrome is the most common cause of intellectual disability (mental retardation) worldwide. People who have fragile X have a defective gene on the X chromosome. Those who have the defective gene do not always have intellectual disability, but the genetic abnormality can worsen with each successive generation; hence, a woman whose POI is caused by a change in the fragile X gene is at risk of having an intellectually disabled baby, if she is able to conceive and give birth. For this reason, women who are carriers for the abnormality in the fragile X gene are advised to undergo genetic counseling before trying to get pregnant.
●Other chromosomal and genetic causes – Several other chromosomal and genetic abnormalities can lead to POI. For example, some women have Y chromosome material, even though the Y chromosome should exist only in men. Although this condition is rare, women who have Y chromosome material need to have their ovaries removed because the abnormality can cause ovarian tumors. Other genetic abnormalities that can cause POI include those that impair normal hormonal function.
Toxic causes — The most common causes of toxin-induced ovarian insufficiency are chemotherapy drugs and radiation therapy, both of which are used to treat cancer (see "Ovarian failure due to anticancer drugs and radiation").
Autoimmune causes — The job of the immune system is to identify and destroy foreign or abnormal cells that can cause infection, cancer, or other problems. Unfortunately, the immune system sometimes misdirects its efforts and begins attacking the body's normal, healthy cells. In some cases of POI, the immune system mistakenly attacks hormone-producing (endocrine) organs, including not only the ovaries but also the adrenal glands, the thyroid glands, and other structures.
Women whose ovarian insufficiency is caused by an autoimmune disorder should have their adrenal and thyroid function evaluated. If the adrenal glands are affected, it can cause a very serious and potentially life-threatening condition called primary adrenal insufficiency (Addison's disease). (See "Patient information: Adrenal insufficiency (Addison's disease) (Beyond the Basics)".)
PRIMARY OVARIAN INSUFFICIENCY SYMPTOMS
Most women with primary ovarian insufficiency (POI) undergo a normal puberty and have regular periods before developing ovarian insufficiency. The most common symptom that prompts them to seek medical care is missed or infrequent periods.
Some women first notice that their periods are infrequent or absent when they stop taking birth control pills, but that does not mean that the pills caused POI. While taking the pill may mask the condition, it cannot cause it.
Other POI symptoms include hot flashes or vaginal dryness, because women eventually produce little or no estrogen. As the condition progresses, some women may also develop vaginal inflammation and thinning of the vaginal walls, which can make intercourse painful.
Family planning — POI often interferes with a woman's ability to get pregnant. Even so, between 5 and 10 percent of women with the condition are able to conceive and give birth normally. Others become pregnant through in vitro fertilization (IVF) using donor eggs. (See 'Infertility treatment' below.)
PRIMARY OVARIAN INSUFFICIENCY DIAGNOSIS
If you are younger than 40 years and have not had a regular period for three months or longer, see a healthcare provider for a full evaluation.
Even if you do not want to get pregnant, the condition can have broad-reaching implications for your overall health. Women with primary ovarian insufficiency (POI) are at increased risk for osteoporosis and possibly even heart disease, so it's important that the condition be detected early and managed appropriately.
To determine the cause of your irregular, absent, or unusually light periods, your healthcare provider should ask whether:
●You have symptoms besides light, irregular, or absent periods. Some women with POI have hot flashes or vaginal dryness, and these symptoms hold clues about how the ovaries are working.
●You have had surgery on your ovaries, or received chemotherapy or radiation therapy, as these all damage ovarian tissue. (See "Ovarian failure due to anticancer drugs and radiation".)
●You or any of your family members have any autoimmune diseases, such as polyglandular failure, hypothyroidism, Addison disease, vitiligo, myasthenia gravis, Graves' disease, Sjögren syndrome, lupus, hypoparathyroidism, recurrent mucocutaneous candidiasis, celiac disease, type 1 diabetes, or rheumatoid arthritis. A personal or family history of these conditions can point to autoimmune ovarian insufficiency. (See "Clinical features and diagnosis of autoimmune primary ovarian insufficiency (premature ovarian failure)".)
●You have any symptoms of adrenal insufficiency, such as decreased appetite, weight loss, vague abdominal pain, weakness, fatigue, salt craving, or darkening of the skin. These symptoms are important, because roughly 3 percent of women with POI develop adrenal insufficiency. (See "Clinical manifestations of adrenal insufficiency in adults".)
●Any of your family members have POI. Approximately 10 percent of cases of ovarian insufficiency run in families.
●You have a family history of fragile X syndrome, intellectual disability (mental retardation), or developmental delay. A family history of these conditions suggests that fragile X syndrome could be involved in your diagnosis.
●You have any hearing loss, because some genetic causes of POI can cause deafness.
Important tests — In addition to asking you detailed questions about your personal and family history, and performing a physical examination, your healthcare provider should order a blood test to measure various hormone levels.
To be diagnosed with POI, you must have elevated levels of a hormone called follicle stimulating hormone (FSH). High levels of FSH indicate that your brain is trying to stimulate the ovaries but the ovaries are not responding. That's important because the ovaries sometimes fail not because they are dysfunctional, but because the brain or the body's master gland, the pituitary, has stopped properly regulating ovarian function.
If blood tests confirm that you have POI, your healthcare provider should then look for a potential cause. Tests used to determine the cause of the disorder include:
●Karyotyping, which determines whether any chromosomal abnormalities exist.
●Testing for antibodies against the adrenal gland, which determines if you have a specific type of ovarian autoimmunity.
●Testing for the FMR1 premutation, a genetic test to determine if you have a specific form of POI.
PRIMARY OVARIAN INSUFFICIENCY TREATMENT
Taking care of you — The diagnosis is more than infertility and affects a woman's physical and emotional well-being. Management of the condition must address both . Before deciding about your plans for a family, it is first important to be healthy yourself. There are multiple choices available to you if you decide you want to become a parent.
Estrogen replacement — One of the main goals of primary ovarian insufficiency (POI) treatment is replacing the estrogen that the ovaries have stopped producing. That's important, because estrogen is vital to certain normal processes. The bones, for example, need estrogen stimulation to stay strong and resistant to fracture. Without estrogen, women with POI are at risk of developing the bone-thinning disease osteoporosis.
There is also some controversial evidence that a lack of estrogen, particularly before the age of 50 years, can increase the risk of heart disease. What's more, without estrogen, women often develop symptoms of menopause, namely hot flashes, night sweats, sleep disturbance, and vaginal dryness. Estrogen therapy aims to prevent or alleviate all of these consequences of estrogen deficiency. However most women cannot take estrogen alone; they must combine it with a progestin (a form of progesterone) to prevent a condition that could lead to cancer of the uterus.
Most experts currently recommend that women with POI should take estrogen until age 50 years, the average age of menopause. (See "Management of spontaneous primary ovarian insufficiency (premature ovarian failure)".)
Type of estrogen therapy — The main form of estrogen that the ovaries normally produce is called estradiol. Some experts believe that giving women this type of estrogen best mimics the “natural condition,” but other forms of estrogen are available and are also effective.
Women who opt for estradiol can get it in pill form, in a patch that is worn on the skin, or in a ring that is inserted into the vagina. The estradiol patch and vaginal ring may offer advantages over the pill form, including:
●They deliver the same hormone that the ovaries make
●The estrogen does not have to go through the liver to get into the bloodstream
●The estrogen gets into the body in a slow, steady stream, rather than all at once
●The estrogen can be measured easily in the bloodstream
Despite the advantages the patch and ring may have, other forms of estrogen replacement are also effective, and women should choose the form that best suits them. Some women do not like wearing the patch or using the ring; others develop skin irritation when they wear the patch. For them, hormones in pill form may be a better choice. Regardless of the form of estrogen they choose, most women must also take some form of progestin (a type of progesterone). With progestins, women also have choices. They come in patch or pill form and there are synthetic and “natural” versions.
Barrier contraception (eg, condoms) or an intrauterine device (IUD) are the preferred methods for women who wish to avoid pregnancy. The oral contraceptive (birth control pill) has not been demonstrated to be effective in women with POI. The dose may not be high enough for women with POI because of their high follicle-stimulating hormone (FSH) levels. Oral contraceptives work by lowering the FSH level to prevent ovulation. Occasional women with POI have become pregnant in spite of taking the pill (but this has not been carefully studied).
Women who do want to get pregnant, meanwhile, should opt for a hormone combination that changes cyclically, the way estrogen and progestin do naturally. Women with POI commonly experience unpredictable and intermittent ovarian function, and it is estimated that there is a about a 4 percent chance of ovulating each month.
Duration of estrogen therapy — Women taking estrogen and progestin may worry about the risks of hormone replacement therapy. After all, recent studies have linked the use of these hormones with an elevated risk of heart attack, stroke, and breast cancer, among other things. The fact is, those studies looked at the effects of estrogen and progestin in women who were in their sixties and seventies and who had undergone menopause naturally.
The results of those studies do not apply to younger women with POI. On the contrary, studies in women with the condition suggest that they are more likely to have cardiovascular problems if they don't take hormones than if they do. Plus, forgoing hormones can lead to osteoporosis.
Most experts agree, in general, that young women with POI should use hormone therapy at least until they turn 50 years.
Infertility treatment — As noted above, between 5 and 10 percent of women with POI are able to conceive and give birth normally without any special treatment. Treatment with estrogen, fertility drugs, or other hormones, has not been shown to improve fertility.
One treatment that is successful is in vitro fertilization (IVF) with donor eggs. In one report of 61 women with POI undergoing 90 treatment cycles, the cumulative chance of pregnancy after three cycles was approximately 90 percent. Success rates for this procedure depend primarily on the age of the egg donor. Embryo donation, in which frozen embryos are donated to the couple, is also often successful, and in general, less expensive.
If you are interested in becoming pregnant, work with your healthcare provider to identify the cause of your condition before you start trying to conceive. Some underlying causes of POI can adversely affect a pregnancy or a fetus, if a pregnancy is successful. For some women, adoption is a good option.
●Being diagnosed with primary ovarian insufficiency (POI, also called premature ovarian failure) can be emotionally trying. Women with the disorder may need time to grieve and adjust to the diagnosis, and there are resources that can help them do that.
●Women with POI should consider taking estrogen-progestin therapy at least until age 50 years to prevent osteoporosis and possibly cardiovascular disease. Taking these hormones will have the added benefit of reducing menopausal symptoms, including hot flashes, night sweats, and vaginal dryness.
●Women interested in becoming pregnant should consult their own healthcare provider about possible therapeutic options. Those who are comfortable with pursuing assisted reproduction may want to consider in vitro fertilization (IVF) using donor eggs or donor embryos.
WHERE TO GET MORE INFORMATION
Your healthcare provider is the best source of information for questions and concerns related to your medical problem.
This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.
Patient level information — UpToDate offers two types of patient education materials.
The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.
Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.
Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.
Clinical manifestations and diagnosis of Turner syndrome (gonadal dysgenesis)
Etiology, diagnosis, and treatment of secondary amenorrhea
Clinical manifestations and evaluation of spontaneous primary ovarian insufficiency (premature ovarian failure)
Patterns of relapse and long-term complications of therapy in breast cancer survivors
Management of spontaneous primary ovarian insufficiency (premature ovarian failure)
Management of Turner syndrome (gonadal dysgenesis)
Ovarian failure due to anticancer drugs and radiation
Pathogenesis and causes of spontaneous primary ovarian insufficiency (premature ovarian failure)
Clinical features and diagnosis of autoimmune primary ovarian insufficiency (premature ovarian failure)
Clinical manifestations of adrenal insufficiency in adults
The following organizations also provide reliable health information.
●National Library of Medicine
●American Society for Reproductive Medicine
●Resolve: The National Infertility Association
- Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009; 360:606.
- Groff AA, Covington SN, Halverson LR, et al. Assessing the emotional needs of women with spontaneous premature ovarian failure. Fertil Steril 2005; 83:1734.
- Sterling EW, Nelson LM. From victim to survivor to thriver: helping women with primary ovarian insufficiency integrate recovery, self-management, and wellness. Semin Reprod Med 2011; 29:353.
All topics are updated as new information becomes available. Our peer review process typically takes one to six weeks depending on the issue.