What Is Primary Ovarian Insufficiency?
is a disorder that involves dysfunction of the ovaries that leads to decreased estrogen and eventually, the loss of residual follicles in the ovaries in patients before the age of 40. Because of this loss, there is amenorrhea and infertility.
Among females who have primary amenorrhea, 10-28% of the time, the cause is Primary Ovarian Insufficiency. For patients with secondary amenorrhea, POI counts for 4-18% of the causes. (1)
The first case of Primary Ovarian Insufficiency was noted in 1942 by Fuller Albright who gave the term “Primary Ovarian Insufficiency” to the condition.
What are the Causes of Primary Ovarian Insufficiency
The cause of Primary Ovarian Insufficiency is unknown but underlying causes range from genetic abnormalities, metabolic disorders, autoimmunity, infections, iatrogenic procedures, and environmental factors.
Genetic abnormalities have been noted to be the cause of POI 10.8% at a time (2) and can be further divided into either a genetic or chromosomal abnormality.
The most common for chromosomal abnormalities is Turner Syndrome, a disease that clinically manifests with primary amenorrhea, short stature, and webbing of the neck.
Autoimmunity causes POI 30% of the time and may coexist with other disorders of the endocrine like adrenal insufficiency, type 1 diabetes mellitus and Hashimoto’s thyroiditis. POI occurs with autoimmune diseases like rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, multiple sclerosis, myasthenia gravis and Sjögren’s syndrome.
Patients who have iatrogenic causes of POI are often seen in oncologic patients who have been treated with chemotherapy and radiation. The risk for POI during chemotherapy or radiation increases with age after puberty especially when high dose chemotherapy regimens are used or for those who have combined chemotherapy and radiation as treatments.
Surgeries may also be an iatrogenic cause of POI as seen in patients who undergo excision of ovaries or to those with surgeries that result in a decreased blood supply of the gonads.
Viruses that may cause POI are parotitis which may lead to mumps oophoritis and further complicate into ovarian failure, but this is uncommon since most women recover their normal organ function after an infection. The second virus that is known to cause POI is the human immunodeficiency virus (HIV) and the antiretroviral treatment given to HIV patients may also damage ovarian functions.
Environmental factors (3) that may cause POI are toxins and pollutants such as Bisphenol A, pesticides, cigarette smoke , polycyclic aromatic hydrocarbons, and dioxins.
For patients with POI, about 76% of them have normal (4), regular menses during puberty and adulthood but then followed by disruptions in their menses. Sadly, ovarian function in patients with POI is unpredictable.
What are the Symptoms of Primary Ovarian Insufficiency
Clinical symptoms of patients with Primary Ovarian Insufficiency may be any of the following:
- Night sweats
- Hot flushes
- Painful sexual intercourse
- Dryness of the vaginal area
- Disturbance in sleep
- Mood changes
- Lack of energy
- Altered urinary function
- Problems in concentration
These symptoms occur with variability in severity since there can be fluctuations in ovarian activity. Primary Ovarian Insufficiency is devastating because it decreases the quality of life of any woman affected by it not only because of the symptoms but also because of the other risks it poses like osteoporosis due to reduced bone mineral density, increased cardiovascular risk, and atrophic changes in the genital and urinary system.
Patients affected with POI also suffer from the negative impact of the disease psychologically from repetitive failure in conceiving and lower sexual life satisfaction.
How to Diagnose POI
Diagnosis of POI is the occurrence of the symptoms mentioned above and amenorrhea (no menstruation) or rare menstruation that occurs for at least four months in a patient 40 years old or below.
Patients will be requested for FSH (Follicle Stimulating Hormone) level at a four-week interval because this is the gold standard test for a diagnosis of POI. Other blood tests may also be requested by your physician.
Presently, no proven treatment to restore the normal function of the ovaries has been discovered but some treatments can improve the symptoms and other risk factors associated with Primary Ovarian Insufficiency.
It is important to know however that 5 to 10% of women who have POI can successfully conceive without medical intervention. (5) This is because there are cases of Primary Ovarian Insufficiencies that still retain some of the ovary’s functions and it is called “spontaneous remission.” This means that the ovaries go back to functioning normally and once fertility is restored, patients can get pregnant again. (5)
What are Some Treatments for POI
Hormone Replacement Therapy (HRT) is the most common treatment given to patients with POI. HRT, as the name suggests gives the body estrogen and other hormones that should have been present in the body but the ovaries cannot produce.
This therapy improves symptoms such as dryness of the vagina, hot flashes, night sweats, sexual dysfunctions and decreases the risk for osteoporosis and cardiovascular diseases (heart attack and hypertension).
Hormone Replacement Therapy allows women with POI to have a regular period. Evidence also shows that it improves pregnancy rates of patients by stimulating ovulation.
HRT for POI usually uses a combination of progestin (a type of progesterone) and estrogen. It can come in the form of pills, gels, patches, cream, vaginal ring, or an intrauterine device. Patients are often advised to undergo Hormone Replacement Therapy until they are 50 years of age, which is the typical age when menopause begins.
HRT provides minimal side effects and is recommended for women with POI to help address symptoms that are associated with it. HRT of patients with POI is different from hormone therapies given to patients with menopause or other disease entities, which is why it is important to visit your health care provider first before taking these medications.
Patients with POI are also given calcium and vitamin D supplements. They should have at least 1,200 mg to 1,500 mg of elemental calcium and 1,000 IU of vitamin D, this is to help avoid osteoporosis. Your doctor may suggest a bone mineral density check to see if you are at risk for osteoporosis and how aggressive your treatment may be for it.
A healthy body weight and regular exercise are also recommended for patients with POI. A normal body weight will decrease the risk for cardiovascular risk and regular exercise helps decrease both weight and prevents osteoporosis.
Overall, Primary Ovarian Insufficiency remains a medical problem that can significantly affect a woman’s life since it’s pathology and treatment are still undergoing clinical investigations. It is important to catch the disease early on to prevent further complications which is why, if you have any of the above symptoms, visiting your physician is necessary.
✔️ Medically Reviewed by Banafsheh Kashani, MD, FACOG
Banafsheh Kashani, M.D., FACOG is a board-certified OB/GYN and specialist in reproductive endocrinology and infertility at Eden Fertility Centers, and has been treating couples and individuals with infertility since 2014. Prior to joining Eden Centers for Advanced Fertility, she was practicing as a top fertility specialist at Kaiser Permanente in Orange County and Reproductive Fertility Center. Dr. Kashani has received numerous awards throughout her years of study and medical training.
Dr. Kashani has conducted extensive research in female reproduction, with a specific focus on the endometrium and implantation. Additionally, Dr. Kashani has authored papers in the areas of fertility preservation, and fertility in women with PCOS and Turners syndrome. She also was part of a large SART-CORS study evaluating the trend in frozen embryo transfers and success rates.
Dr. Kashani is a fellow of the American Congress of Obstetricians and Gynecologists. In addition, she is a diplomat of the American Board of Obstetrics and Gynecology and an active member of the American Society of Reproductive Medicine (ASRM) and Pacific Coast Reproductive Society (PCRS). She is also a member of the Society of Reproductive Endocrinology and Infertility (SREI).