Premature Ovarian Failure – Causes & Symptoms

By MD, PhD, MSc (gynecologist), (embryologist), (gynecologist) and (invitra staff).
Last Update: 10/16/2020

Premature ovarian failure (POF) is the cease of ovarian activity at an early age, before entering in the menopause age, approximately at age 40. This means that the ovaries stop working before you reach menopause. Therefore, the woman does not ovulate and her blood levels of estrogen and progesterone decrease.

The symptoms of POF are not much different from those a woman has when her period disappears, because the symptoms are due to a lack of estrogen.

The cause of this ovarian failure is usually unknown, although there is a greater risk when there is a history of POF in immediate family members.

Formation and exhaustion of the eggs

Ovarian differentiation in the female fetus begins around the eighth week of gestation. Thus, by the 20th week of gestation, there are already about 6-7 million Oogonia (the stem cells that will give rise to the eggs) in the ovaries.

These Oogonia will undergo atresia (die) and their number will decrease until they are born. By the time of puberty, about 300,000 eggs will be released into the menstrual cycles during the course of a woman's reproductive life. In theory, women have enough eggs at birth to release at least until age 50.

Thus, when menstruation stops due to a follicular exhaustion of the ovary before the age of 40, or if there is a lack of response of the ovarian follicles to the hormonal stimuli of the gonadotropins during an assisted reproduction treatment, we will speak of premature ovarian failure.

Early ovarian failure occurs in 1 in 100 women under 40 and 1 in 1000 women under 30.

Causes of POF

In 90% of cases of POF the exact cause is unknown. There are numerous factors that cause this insufficiency in the ovaries, although they are difficult to determine.

The possible causes of POF are described below:

  • Chromosomal defects, such as X-fragile syndrome, Turner syndrome, or other gene alterations.
  • Exposure to toxins such as chemotherapy and radiation therapy.
  • Enzymatic or metabolic defects (galactosemia, hemochromatosis, etc.).
  • Autoimmune diseases such as hypothyroidism (a disease caused by low levels of thyroid hormones).
  • Herpes Zoster or cytomegalovirus infections.

Risk Factors

Factors that increase the risk of developing POF include the following:

Age
the risk of POF increases between the ages of 35 and 40, although it can also occur in younger women.
Family history
if there are other cases of POF running in the family, the risk may increase.
Diseases requiring surgery
is the case of endometriosis for example.

Symptoms

Generally, the symptoms of POF are often similar to those of menopause, as they result from low levels of estrogen.

The absence of menstruation (amenorrhea) is the most striking factor for a young woman and is the main reason for consultation.

Specifically, we speak of premature ovarian failure when a woman under 40 years of age presents amenorrhea, very low levels of estrogens and levels of gonadotropins above 40 mIU/mL.

Other symptoms associated with low estrogen levels include the following:

  • Irregular bleeding or no monthly bleeding.
  • Night sweats.
  • Vaginal dryness.
  • Hot flushes or hot flashes.
  • Sleep disorders and insomnia.
  • Irritability and susceptibility.
  • Lack of libido.
  • Difficulty concentrating.
  • Fertility problems.

Consequences

In addition to the symptoms and discomfort we have discussed in the previous section, POF also has long-term consequences for the women's health.

There are various hormones in the body whose values are diminished due to early ovarian failure. Therefore, there is a greater risk of suffering from other conditions such as those discussed below:

Anxiety and depression
due to unexpected loss of ovarian function. In these cases, a visit to a psychologist is recommended.
Dry eye syndrome
causes discomfort and blurred vision.
Cardiopathies
low estrogen levels have effects on the muscles surrounding the arteries and on the buildup of cholesterol in them. All of which increases the risk of heart attacks.
Osteoporosis
this is a skeletal disease in which there is a decrease in bone mass density. Therefore, there is a greater chance of suffering fractures in the bones.

Diagnosis of POF

The first warning sign in women is the disappearance of menstruation or the alteration of menstrual periods. To clarify this cause, a gynecological examination is most recommended in this case. The doctor takes a medical history along with a physical and gynecological examination.

To confirm the presence of POF, an analysis of the FSH and estradiol hormones is performed. An elevated FSH and low estradiol establishes evidence of ovarian failure. These determinations will be repeated on more than one occasion to confirm the diagnosis.

On the other hand, if the ovarian failure has no apparent reason, a blood test can be performed to study the karyotype, that is, the set of chromosomes that each cell has. In this way, it will be possible to determine whether the cause of POF is a chromosomal alteration.

Treatment

As POF can affect both physical and emotional health, multidisciplinary treatment should be established and even a visit to the psychologist should be made.

Hormone replacement therapy using estrogen and progesterone pills or patches is the most widely used. This therapy relieves menopausal symptoms and helps combat bone loss caused by osteoporosis.

In terms of preventing osteoporosis, women with POF should consume an adequate amount of calcium and vitamin D. In addition, regular physical activity and weight control are important. This also avoids suffering from coronary disease.

Effects of POF on fertility

Patients with POF often have fertility problems caused by a lack of ovulation and low estrogen levels. In these cases, ovarian stimulation for in vitro fertilization treatment with one's own eggs is usually not effective.

However, some women in their 30s and 40s can get good embryos through IVF with their own eggs, even if the number of eggs obtained is small. Another option is to perform an oocyte collection. If a positive result is not achieved in this way, it should already be passed on to egg donation.

Finally, in 5-10% of cases, a pregnancy can be achieved if the alteration is not permanent and the ovary may have some activity. For this, the ovarian failure must be spontaneous and the karyotype normal. However, there's no way of knowing if this is going to happen.

FAQs from users

What is premature ovarian failure (POF)?

By Blanca Paraíso MD, PhD, MSc (gynecologist).

A woman is considered to have POF if she has deteriorated ovarian function under 40 years of age. Some time ago this was also known as early ovarian failure or early menopause. However, these terms are not entirely accurate, because at menopause there is a total or almost total depletion of the ovarian reserve, so menstruation disappears completely. In early ovarian failure patients may continue to ovulate occasionally.
Read more

Can premature ovarian failure be prevented?

By Dra. Rut Gómez de Segura (gynecologist).

Premature ovarian failure is the decrease or lack of oocytes (eggs) in patients under 40 years of age. Prevention of POF depends on the cause of the failure. Usually, POF has no known cause, so it cannot be prevented.

Instead, there are times when POF is caused by genetic factors, autoimmune factors, metabolic factors, infections, toxins, or medication.
Read more

Can you get pregnant having POF?

By Blanca Paraíso MD, PhD, MSc (gynecologist).

Yes, in up to 5-10% of cases, these patients can become pregnant spontaneously after a single ovulation. However, the vast majority of them will present sterility and will have to resort to egg donation.
Read more

What care should women with POF follow?

By Marta Barranquero Gómez (embryologist).

Women with POF should lead a healthy lifestyle with a balanced diet and moderate physical exercise. They can also get help from a professional to look after their mental and emotional health.

Is premature ovarian failure reversible?

By Marta Barranquero Gómez (embryologist).

No. Women with ovarian insufficiency will hardly be able to regain normal ovarian function.

However, in some cases the ovary may have some intermittent activity, so these women may have spontaneous ovulations and even become pregnant.

Suggested for you

For more information on other hormonal disorders in women that cause endocrine-ovarian factor infertility, I invite you to click on the following link: What are the endocrine causes of female infertility?

If you also want to learn more about assisted reproduction techniques, you can visit the following article: What are infertiltiy treatments? Definition, types & costs.

Our editors have made great efforts to create this content for you. By sharing this post, you are helping us to keep ourselves motivated to work even harder.

References

Llano E, Gomez-H L, García-Tuñón I, Sánchez-Martín M, Caburet S, Barbero JL, Schimenti JC, Veitia RA, Pendas AM. STAG3 is a strong candidate gene for male infertility. Hum Mol Genet. 2014;23(13):3421-31.

Caburet S, Arboleda VA, Llano E, Overbeek PA, Barbero JL, Oka K, Harrison W, Vaiman D, Ben-Neriah Z, García-Tuñón I, Fellous M, Pendás AM, Veitia RA, Vilain E. Mutant cohesin in premature ovarian failure. N Engl J Med. 2014;370(10):943-949.

Juárez K, Lara R, García J. Insuficiencia ovárica prematura: una revisión. Rev. chil. obstet. ginecol. 2012 vol.77(2): 148 - 153. doi:10.4067/S0717-75262012000200012.

Maclaran K, Panay N. Current concepts in premature ovarian insufficiency. Women´s Health 11(2):169–182, 2015.

Kirshenbaum M1, Orvieto R. Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal. J Assist Reprod Genet. 2019 Aug 22. doi: 10.1007/s10815-019-01572-0.

Nappi RE, Cucinella L, Martini E, Rossi M, Tiranini L, Martella S, Bosoni D, Cassani C. Sexuality in premature ovarian insufficiency. Climacteric. 2019 Jun;22(3):289-295. doi: 10.1080/13697137.2019.1575356.

Ni Y, Xu D, Lv F, Wan Y, Fan G, Zou W, Chen Y, Pei LG, Yang J, Wang H. Prenatal ethanol exposure induces susceptibility to premature ovarian insufficiency. J Endocrinol. 2019 Jul 1. pii: JOE-19-0063.R1. doi: 10.1530/JOE-19-0063.

FAQs from users: 'What is premature ovarian failure (POF)?', 'Can premature ovarian failure be prevented?', 'Can you get pregnant having POF?', 'What care should women with POF follow?' and 'Is premature ovarian failure reversible?'.

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Authors and contributors

 Blanca Paraíso
Blanca Paraíso
MD, PhD, MSc
Gynecologist
Bachelor's Degree in Medicine and Ph.D from the Complutense University of Madrid (UCM). Postgraduate Course in Statistics of Health Sciences. Doctor specialized in Obstetrics & Gynecology, and Assisted Procreation. More information about Blanca Paraíso
License: 454505579
 Marta Barranquero Gómez
Marta Barranquero Gómez
Embryologist
Graduated in Biochemistry and Biomedical Sciences by the University of Valencia (UV) and specialized in Assisted Reproduction by the University of Alcalá de Henares (UAH) in collaboration with Ginefiv and in Clinical Genetics by the University of Alcalá de Henares (UAH). More information about Marta Barranquero Gómez
License: 3316-CV
Dra. Rut Gómez de Segura
Dra. Rut Gómez de Segura
Gynecologist
Graduation in Medicine and Surgery from the University of Alcalá de Henares. Specialization in Obstetrics and Gynecology at the Hospital Costa del Sol in Marbella. Dr Rut Gómez de Segura currently works as medical director in the fertility center ProcreaTec in Madrid. More information about Dra. Rut Gómez de Segura
Licence number: 28/2908776
Adapted into english by:
 Romina Packan
Romina Packan
inviTRA Staff
Editor and translator for the English and German edition of inviTRA. More information about Romina Packan

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