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Primary Ovarian Insufficiency: Causes, Impact on Fertility and Periods, & How to Treat

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Last updated February 11, 2021

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This article will cover the symptoms, causes, and management of primary ovarian insufficiency. Primary ovarian insufficiency is a loss of normal function of the ovaries before age 40, also known as early menopause.

What is primary ovarian insufficiency?

Primary ovarian insufficiency is the loss of normal ovarian function and reduced fertility before 40 years of age. In some women, these symptoms can begin as early as teenage years. The term “insufficiency” is preferred over “failure” in that ovarian function is unpredictable. Five to 10% of women with primary ovarian insufficiency successfully conceive children.

Symptoms include irregular periods or a loss of periods, hot flashes, night sweats, decreased sexual desire, vaginal dryness, difficulty getting pregnant and difficulty concentrating.

Treatment focuses on addressing symptoms with estrogen therapy and other supplements. Further support may be necessary for some women who wish to have children.

If you are experiencing symptoms of primary ovarian insufficiency, or are otherwise concerned about your menstrual cycle, you should consult your physician for appropriate care.

Symptoms of primary ovarian insufficiency

Main symptoms

Symptoms of primary ovarian insufficiency are very similar to symptoms of menopause (even though they are not the same condition). The signs are similar because primary ovarian insufficiency and menopause are both the result of a lack/deficiency of estrogen created by the ovaries. These signs and symptoms include:

  • Irregular or absent periods: Irregular periods or a complete loss of periods (amenorrhea) that lasts for multiple years in the absence of birth control are the most common symptoms of primary ovarian insufficiency that lead women to go to their physician.
  • Hot flashes
  • Night sweats
  • Decreased sexual desire
  • Vaginal dryness
  • Difficulty getting pregnant
  • Difficulty concentrating


Complications of primary ovarian insufficiency may include the following.

  • Osteoporosis: Osteoporosis is a condition of weak, brittle bones that results from low estrogen levels. Estrogen is necessary for maintaining strong, healthy bones, thus, women with primary ovarian insufficiency are at risk for easily breaking their bones.
  • Infertility: Often the most distressing complication of primary ovarian insufficiency for many women is difficulty getting pregnant.
  • Heart disease: Low levels of estrogen can affect the muscles lining the arteries of the heart and can increase the buildup of cholesterol inside the vessels. These factors increase your risk of atherosclerosis (hardening of the arteries) and resultant heart disease.
  • Anxiety and depression: The complications of this condition in addition to already low estrogen levels can cause some women to become depressed and anxious about their situation.
  • Hypoparathyroidism: Twenty percent of people with primary ovarian insufficiency will experience hypoparathyroidism. “Hypo” means “low levels of” and parathyroid hormone is an essential hormone that regulates calcium levels in the blood.
  • Adrenal insufficiency: Fifty percent of women with primary ovarian insufficiency develop adrenal insufficiency. The adrenal gland produces the essential hormones adrenaline, cortisol, and aldosterone.

Causes of primary ovarian insufficiency

The female reproductive cycle is a complex sequence of hormonal changes and events all with the goal of creating and sustaining the ideal environment for conceiving and nurturing a potential fetus. Primary ovarian insufficiency can hinder both short- and long-term health and family expectations of women experiencing it.

About the female reproductive cycle

The cycle begins with the ovaries. The ovaries produce estrogen that initiates the cycle. Ovaries are also where all female reproductive eggs, or oocytes, are stored. Each month, a single egg is released from the ovary into the fallopian tube, where fertilization with male sperm is possible. If the egg is fertilized, the fertilized egg (now called a zygote) will then move to the uterus where the lining has thickened in preparation for implantation, where the lining gives energy to the zygote. The uterus will then continue to expand and thicken as the fetus grows within.

However, in the absence of pregnancy, when fertilization does not occur, the blood and thickened tissue that lines the uterus will shed through the vagina. This is known as menses. Other terms for menses include menstruation, menstrual cycle and period.

Women will continue experiencing this cycle, whether it ends in menses or pregnancy until the ovaries reduce their production of estrogen — a natural phenomenon called menopause. Menopause is the cessation of menstruation and usually occurs at an average of 52 years of age. Many women start this transition to menopause and naturally begin to experience reduced fertility at around 40 years of age.

Causes details

Primary ovarian insufficiency is caused by a loss of estrogen production by the ovaries. It can be caused by the following:

  • Chromosomal defects: Certain genetic disorders that affect the X chromosome (such as Turner’s Syndrome and Fragile X) are closely associated with primary ovarian insufficiency in adolescents.
  • Chemotherapy or radiation therapy: Chemotherapy and radiation therapy are the most common causes of acute ovarian failure. These therapies damage the genetic material in cells and have a preference for ovarian cells.
  • Immunological dysfunction: Four percent of women found to have primary ovarian insufficiency not caused by chromosomal abnormalities or chemo/radiation therapy will have ovarian or adrenal autoantibodies, suggesting an autoimmune cause for their disease. An autoimmune disease is one that results in the body’s attack of its own cells.

Who is most likely to be affected

Factors that increase the risk of developing primary ovarian insufficiency include:

  • Age: Risk increases with increasing age and is most common between the ages of 35 and 40. Nevertheless, younger women and adolescents can also develop this condition.
  • Family history: Having a family history of primary ovarian insufficiency increases the risk of developing the disorder.
  • Multiple ovarian surgeries: Repeated surgeries on the ovaries increases the risk of primary ovarian insufficiency.

Treatment options, relief, and prevention for primary ovarian insufficiency

Treatment for primary ovarian insufficiency focuses on addressing the symptoms that occur due to estrogen deficiency.

Estrogen therapy

Replacing estrogen can increase the body’s levels and prevent osteoporosis. Estrogen administration can also relieve symptoms such as hot flashes and dryness. Your physician will prescribe estrogen with another hormone called progesterone in order to protect the lining of the uterus from changes that can lead to cancer when too much estrogen is given alone. Long-term estrogen plus progesterone therapy has been linked to an increased risk of cardiovascular disease and breast cancer. In young women with primary ovarian insufficiency, however, the benefits of hormone therapy outweigh the potential risks.

Calcium and vitamin D supplements

Both of these compounds are important for preventing osteoporosis. Since you might not get enough in your diet or from exposure to sunlight, your physician may decide to start supplements if your baseline bone density is found to be low. Unfortunately, there is no straightforward solution for the fertility issues related to primary ovarian insufficiency. Fertility cannot be restored but you can discuss with your physician other options for pregnancy such as in vitro fertilization and alternatives for children like adoption or surrogacy.


Unfortunately, there is no straightforward solution for the fertility issues related to primary ovarian insufficiency. Fertility cannot be restored but you can discuss with your physician other options for pregnancy such as in vitro fertilization and alternatives for children like adoption or surrogacy.

When to seek further consultation for primary ovarian insufficiency

If you have not had a period for more than three months you should make an appointment with your physician promptly to determine the cause. There are many reasons for not having a period other than primary ovarian insufficiency, including pregnancy, stress, and changes in diet or exercise. All of these potential causes all need to be evaluated in order to receive proper treatment.

Even if you welcome the break from monthly periods, it is important to see your physician anyway to determine what is causing the change given that reproductive issues can have multiple, serious complications.

Share your story

Dr. Gambrah-Lyles is a resident pediatrician at the Children's Hospital of Philadelphia. She is a graduate of the University of Pennsylvania Perelman School of Medicine (2019). She graduated cum laude and received her undergraduate degree in Biochemistry and Spanish from Washington University in St. Louis (2013). Her research explores the intersections between neurology, public health, and infectious disease. She has investigated nutrition and cerebral palsy in Botswana, and completed a year-long project in Brazil, researching growth and developmental outcomes of Zika virus infection in pediatric patients as a Doris Duke International Scholar. Dr. Gambrah-Lyles speaks four languages, loves staying active, and enjoys sharing her love for medicine through teaching and writing.

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