Premature Ovarian Failure (Early Menopause, Ovarian Insufficiency)

What is premature ovarian failure?

Premature ovarian failure is a condition where the ovaries cease functioning to the same degree as it would in the reproductive years of life. This decline in ovarian function is seen in lower than normal female sex hormone levels, disruption in the menstrual cycle and difficulty in falling pregnant. It is essentially the same process that is seen in menopause but for it to be considered premature, it has to occur before 40 years of age. Therefore the condition is also known as premature menopause or early menopause.

Premature Ovarian Failure vs Menopause

Although the term early menopause and premature menopause are often used to describe premature ovarian failure, the fact is that this condition is not menopause as such, irrespective of the woman’s age. In menopause, ovarian function declines permanently for life. It is a normal physiological process that affects most women between the age of 45 to 55 years.

However, in premature ovarian failure there are episodes where the ovarian function can restore again, almost to normal levels for short periods, only to decline thereafter. Women with premature ovarian failure can therefore find that their menstrual cycle returns to normal for these short periods and it is possible that they may even fall pregnant in these times. Therefore premature ovarian failure is not true menopause at an early age.

Even the term ovarian failure can be misleading at times. In the true sense, the ovaries do not fail entirely but rather function less effectively and the term ovarian insufficiency is often preferred. With a deeper understanding of ovarian insufficiency, premature ovarian failure is one type of ovarian insufficiency. However, for most patients the conditions are essentially though to be the same and broadly labeled as premature or early menopause.

How common is premature ovarian failure?

Premature ovarian failure is more common in women as they approach 40 years of age. In the United States, it affects about 1 in 1,000 women before the age of 30 years and may be as prevalent as 1 in 100 women by the age of 40 years. It is often mistaken that ovarian insufficiency only affects adult females but it can occur in teen girls. According to the Royal College of Obstetricians and Gynecologists (UK), premature ovarian failure is on the rise.

How do the ovaries stop functioning?

Premature ovarian failure has a myriad of factors that contribute to the decline in ovarian function. In order to understand the different types of ovary insufficiency, it is important to have a basic knowledge of ovarian function. The ovaries house the egg cells (ova) which are released at the time of ovulation, prior to menstruation. In addition the ovaries have an endocrine function in that it produces and secretes two hormones, primarily estrogen and progesterone.

Hormones

The ovaries are stimulated and regulated by follicle stimulating hormone (FSH) and luteinizing hormone (LH), two gonadotropin hormones secreted from the pituitary gland. These levels of these two hormones are in turn controlled by gonadotropin-releasing hormone (GnRH) produced and secreted from the hypothalamus. GnRH secretion is in turn regulated by other factors like the levels of the estrogens in the bloodstream. It is therefore possible for ovarian dysfunction to arise at the level of the ovary itself, pituitary gland or hypothalamus apart from possible external factors.

Follicles

In many cases where the problem lies in the ovaries itself (primary ovarian insufficiency) with no other causes, the ovarian follicles may either be depleted or dysfunctional. These follicles contain the ova (egg cells), which is released into the fallopian tubes at the time of ovulation. Women have a certain number of follicles but it is usually abundant to last through the reproductive years of life. However, sometimes the number of viable follicles are exhausted or do not function (egg cell release and hormone production) as it should.

Types of Ovarian Insufficiency

Ovarian insufficiency can be categorized as primary or secondary. In primary ovarian sufficiency it is the ovaries itself that stop functioning as normal, often for unknown reasons. In secondary ovarian insufficiency, the ovaries stop functioning appropriately due to problems with the gonadotropins (FSH or LH), gonadotropin-releasing hormone (GnRH) or other disease that affect ovarian function. Primary ovarian insufficiency can in turn be divided into different types.

Occult Primary Ovarian Insufficiency

Normal levels of FSH in the bloodstream but ovaries do not respond as it should.
Even higher levels of FSH do not stimulate the ovaries.
Fertility is reduced but pregnancy is possible.

Biochemical Primary Ovarian Insufficiency

Elevated levels of FSH in the bloodstream.
As with the occult type, higher levels of FSH do not stimulate the ovaries.
Fertility is reduced but pregnancy still possible.

Overt Primary Ovarian Insufficiency

Elevated levels of FSH in the bloodstream.
Menstrual disturbances similar to perimenopause with infrequent, excessive, very light or heavy periods.
Pregnancy is still possible.
Used to be previously known as premature ovarian failure or early menopause.

Premature Ovarian Insufficiency

Elevated gonadotropin levels.
Complete cessation of periods (amenorrhea).
Pregnancy is not possible.
Irreversible type of primary ovarian insufficiency.

Signs and Symptoms

The signs and symptoms of premature ovarian failure are largely the same as perimenopause and menopause. These symptoms includes :

Irregular or missed periods (amenorrhea)
Hot flashes (flushes) with or without night sweats.
Diminished libido.
Vaginal dryness.
Difficulty falling pregnant or inability to conceive (infertility).

There may be other symptoms present as a result of the underlying cause in secondary ovarian insufficiency, and with the complications that may arise with the lower estrogen levels.

Complications of Premature Menopause

The complications of premature ovarian failure are the same as in menopause due to the low estrogen levels. This includes :

Osteoporosis – frequent bone fractures, pain in the back, hip and legs.
Heart disease – changes in blood pressure, chest pain, shortness of breath and fatigue.
Underactive thyroid – weight gain, fatigue, weakness, constipation and depression.
Depression and anxiety.

Causes and Risks

The causes of premature menopause can be discussed according to primary and secondary ovarian insufficiency. Women who are at risk are those in the 35 to 40 year age group and women with a family history of ovarian insufficiency. Recent studies have found that women who had treatment for childhood cancers are at a higher risk. Although the effect of lifestyle factors have not as yet been proven to play a direct role in the condition, it may contribute to the development other illnesses that may cause secondary ovarian insufficiency.

Primary Ovarian Insufficiency

Autoimmune disorders that affect the ovaries.
Certain genes.
Iatrogenic – cancer treatment (chemotherapy and radiation therapy) in particular.
Thyroid dysfunction.
Total hysterectomy (where both ovaries are removed).
Unknown causes (idiopathic).

Secondary Ovarian Insufficiency

Certain drugs.
Eating disorders.
Excessive exercise.
Hypothalamic dysfunction and tumors.
Pituitary gland dysfunction and tumors.
Viral infections.

Tests and Diagnosis

The symptoms of menopause that arises before the age of 40 years should warrant further tests before diagnosing premature ovarian failure. Some of these symptoms are seen with pregnancy and may be due to other disorders (secondary ovarian insufficiency). Specific tests that should be conducted includes :

Follicle-stimulating hormone (FSH) levels
Luteinizing hormone (LH) levels
Serum estradiol levels
Karyotype
Ovarian antibodies

Imaging studies like an ultrasound of the ovaries or an MRI (magnetic resonance imaging) scan of the pituitary gland and hypothalamus may also be done to identify problems in these areas that cannot be detected with laboratory tests.

Treatment of Premature Ovarian Failure

In secondary ovarian insufficiency, treatment is directed at the underlying cause. With primary ovarian insufficiency, treatment options include :

Hormone therapy with estrogen and progestin. These hormones can be administered continuously (daily dose) or cyclically (start-stop-start). It helps to ease the symptoms of premature ovarian failure and minimize or even prevent complications.
Androgen (male hormone) replacement is not routinely prescribed but may be considered for severe symptoms that are persistent and do not ease with estrogens.
Calcium and vitamin D supplements are necessary to maintain a normal bone mass density and prevent osteoporosis.
Fertility treatments may be considered for women who wish to fall pregnant. However, there are no specific fertility treatments for premature ovarian failure.

Although diet and exercise itself cannot change premature ovarian failure, it is useful for minimizing the effects of osteoporosis or even prevent it altogether. This includes :

Foods rich in calcium and vitamin D although supplementation is also required.
Adequate sunlight exposure, particularly for women residing in Northern regions.
Weight bearing exercise at least 3 times per week.

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References :

http://www.mayoclinic.com/health/premature-ovarian-failure/DS00843

http://emedicine.medscape.com/article/271046-overview

http://www.rcog.org.uk/news/tog-release-incidence-early-menopause-rise-says-new-review

http://www.nichd.nih.gov/health/topics/premature_ovarian_failure.cfm