Premature Ovarian Failure
What is Premature Ovarian Failure?
Premature Ovarian Failure is a condition characterized by amenorrhea (no menses), low estrogen level and high gonadotrophin levels resulting in menopause-like symptoms in women younger than age 40.
The human ovary function as a reproductive organ storing and producing eggs every month during ovulation to enable fertilization by sperm and to facilitate monthly menses. It also acts as endocrine organ producing female hormones estrogen and progesterone which regulates menses. Predictable monthly menses cycle means the ovaries are healthily functioning during the reproductive years.
Usually the pituitary gland will produce gonadotrophins (Follicle Stimulating Hormone FSH & Luteinizing Hormone LH) which regulate the production of female hormones from the ovaries.
Ageing will be associated with decrease fertility due to the reduce number of eggs in the ovary, menstrual irregularity and reduced hormone productions. Finally menopause is when there is irreversible cessation of menses around age 50.
In patients with premature ovarian failure, the ovaries fail to function properly before the age 40. The ovaries are unable to ovulate and produce normal levels of female hormones. This results in infertility, early menopause and increased risk of osteoporosis. The estimated incidence of premature ovarian failure is 1 in 1000 women younger than 30, 1 in 250 in women by age 35 and 1 in 100 in women by age 40.
What is Premature Ovarian Failure?
Premature Ovarian Failure is a condition characterized by amenorrhea (no menses), low estrogen level and high gonadotrophin levels resulting in menopause-like symptoms in women younger than age 40.
The human ovary function as a reproductive organ storing and producing eggs every month during ovulation to enable fertilization by sperm and to facilitate monthly menses. It also acts as endocrine organ producing female hormones estrogen and progesterone which regulates menses. Predictable monthly menses cycle means the ovaries are healthily functioning during the reproductive years.
Usually the pituitary gland will produce gonadotrophins (Follicle Stimulating Hormone FSH & Luteinizing Hormone LH) which regulate the production of female hormones from the ovaries.
Ageing will be associated with decrease fertility due to the reduce number of eggs in the ovary, menstrual irregularity and reduced hormone productions. Finally menopause is when there is irreversible cessation of menses around age 50.
In patients with premature ovarian failure, the ovaries fail to function properly before the age 40. The ovaries are unable to ovulate and produce normal levels of female hormones. This results in infertility, early menopause and increased risk of osteoporosis. The estimated incidence of premature ovarian failure is 1 in 1000 women younger than 30, 1 in 250 in women by age 35 and 1 in 100 in women by age 40.
What causes Premature Ovarian Failure?
Premature Ovarian Failure will occur when the follicles that carry the egg to be released during ovulation are depleted or disrupted. The exact etiology is still unknown.
Follicles can be depleted in patients with chromosomal defect genetic disorders like Turner’s syndrome and Fragile X Syndrome. Toxins like chemotherapy and radiotherapy treatment to the pelvis may also cause the ovaries to fail as the follicles get depleted.
Follicle dysfunction can occur in autoimmune diseases whereby the body produces antibodies that “attack” own ovarian cells and disrupting the function of follicles.
Premature Ovarian Failure will occur when the follicles that carry the egg to be released during ovulation are depleted or disrupted. The exact etiology is still unknown.
Follicles can be depleted in patients with chromosomal defect genetic disorders like Turner’s syndrome and Fragile X Syndrome. Toxins like chemotherapy and radiotherapy treatment to the pelvis may also cause the ovaries to fail as the follicles get depleted.
Follicle dysfunction can occur in autoimmune diseases whereby the body produces antibodies that “attack” own ovarian cells and disrupting the function of follicles.
Clinical Presentation of Premature Ovarian Failure
The symptoms are similar to patients going through menopause due to the cessation of ovulation and lower estrogen levels. The symptoms patients may experience include:
1. Hot Flushes
2. Night sweats
3. Vaginal dryness with associated dyspareunia (pain during sex)
4. Difficulty concentrating and irritability
5. Reduced sex drive
6. Sleep disturbances
7. Irregular menses or absent menses
8. Infertility due to lack of ovulation
The symptoms are similar to patients going through menopause due to the cessation of ovulation and lower estrogen levels. The symptoms patients may experience include:
1. Hot Flushes
2. Night sweats
3. Vaginal dryness with associated dyspareunia (pain during sex)
4. Difficulty concentrating and irritability
5. Reduced sex drive
6. Sleep disturbances
7. Irregular menses or absent menses
8. Infertility due to lack of ovulation
Complications of Premature Ovarian Failure
1. Osteoporosis: Estrogen hormones are essential for maintaining healthy strong bones. Premature Ovarian Failure patients have low estrogen levels resulting in brittle in bones leading to osteoporosis and increased risk of fractures.
2. Infertility: Lack of monthly ovulation result in infertility
3. Mood Disorders: Infertility and menopause like symptoms will cause women to feel depressed and anxious.
1. Osteoporosis: Estrogen hormones are essential for maintaining healthy strong bones. Premature Ovarian Failure patients have low estrogen levels resulting in brittle in bones leading to osteoporosis and increased risk of fractures.
2. Infertility: Lack of monthly ovulation result in infertility
3. Mood Disorders: Infertility and menopause like symptoms will cause women to feel depressed and anxious.
Tests to diagnose Premature Ovarian Failure
1. Pregnancy test: Woman of reproductive age who present with no menses should have pregnancy excluded.
2. Hormonal levels: In Premature Ovarian Failure, the Follicle Stimulating Hormone FSH levels will be elevated > 40 µIU/mL. Luteinizing Hormone LH levels are lower than FSH levels. The Serum Estradiol (estrogen) levels will be low.
3. Chromosome Karyotyping: Patients suspected of chromosomal defect genetic disorders like Turner’s syndrome and Fragile X Syndrome should be screened.
4. Ovarian Antibodies: Currently there are no affirmative tests for suspected autoimmune cause of Premature Ovarian Failure. Adrenal antibodies can be predictive of autoimmune cause of premature ovarian failure.
5. Thyroid Function Tests: this is done to rule out thyroid disorder that will also cause menses irregularity.
6. Scans: Ultrasound of the ovaries to rule out Polycystic Ovarian Syndrome that can also cause infertility and irregular menses. MRI brain to rule out pituitary tumor is suspected to be the cause for secondary ovarian failure.
Treatment of Premature Ovarian Failure
Treatment addresses the issues that premature ovarian failure caused. Treatment is to replace the hormone estrogen, restore fertility and to take care of the psychological well-being of the patient.
Hormone therapy
Patients should receive cyclical hormone therapy consisting of both estrogen and progestins to relieve the estrogen deficiency menopausal alike symptoms and to maintain bone density preventing osteoporosis.
Estrogen can be given orally or transdermally either continuously or cyclically (21 days on then 7 days off).Estrogen therapy does not prevent pregnancy and ovulation. In fact it lowers Luteinizing Hormone back to normal value improving chance of pregnancy. Oral contraceptives contain more sex steroid than needed for replacement hence not recommended.
Progestins should be given cyclically from day 10-14 days of each month to prevent thickening of the endometrium of the uterus which happens in unopposed estrogen level situations.
Gonadotropin therapy has a theoretical risk of exacerbating autoimmune cause of premature ovarian failure hence not recommended.
Infertility issues
There is no proven treatment to restore the lost ovarian function and restore fertility. Only 5-10% of women with premature ovarian failure will be able to get pregnant. Options available are using donor eggs for In vitro fertilization and other fertility treatment methods best discussed with your gynecologists.
1. Pregnancy test: Woman of reproductive age who present with no menses should have pregnancy excluded.
2. Hormonal levels: In Premature Ovarian Failure, the Follicle Stimulating Hormone FSH levels will be elevated > 40 µIU/mL. Luteinizing Hormone LH levels are lower than FSH levels. The Serum Estradiol (estrogen) levels will be low.
3. Chromosome Karyotyping: Patients suspected of chromosomal defect genetic disorders like Turner’s syndrome and Fragile X Syndrome should be screened.
4. Ovarian Antibodies: Currently there are no affirmative tests for suspected autoimmune cause of Premature Ovarian Failure. Adrenal antibodies can be predictive of autoimmune cause of premature ovarian failure.
5. Thyroid Function Tests: this is done to rule out thyroid disorder that will also cause menses irregularity.
6. Scans: Ultrasound of the ovaries to rule out Polycystic Ovarian Syndrome that can also cause infertility and irregular menses. MRI brain to rule out pituitary tumor is suspected to be the cause for secondary ovarian failure.
Treatment of Premature Ovarian Failure
Treatment addresses the issues that premature ovarian failure caused. Treatment is to replace the hormone estrogen, restore fertility and to take care of the psychological well-being of the patient.
Hormone therapy
Patients should receive cyclical hormone therapy consisting of both estrogen and progestins to relieve the estrogen deficiency menopausal alike symptoms and to maintain bone density preventing osteoporosis.
Estrogen can be given orally or transdermally either continuously or cyclically (21 days on then 7 days off).Estrogen therapy does not prevent pregnancy and ovulation. In fact it lowers Luteinizing Hormone back to normal value improving chance of pregnancy. Oral contraceptives contain more sex steroid than needed for replacement hence not recommended.
Progestins should be given cyclically from day 10-14 days of each month to prevent thickening of the endometrium of the uterus which happens in unopposed estrogen level situations.
Gonadotropin therapy has a theoretical risk of exacerbating autoimmune cause of premature ovarian failure hence not recommended.
Infertility issues
There is no proven treatment to restore the lost ovarian function and restore fertility. Only 5-10% of women with premature ovarian failure will be able to get pregnant. Options available are using donor eggs for In vitro fertilization and other fertility treatment methods best discussed with your gynecologists.
