Premature Ovarian Failure (POF), also known as premature ovarian insufficiency (POI), primary ovarian insufficiency, premature menopause, hypergonadotropic hypogonadism, is the loss of function of the ovaries before age 40.It has been estimated that POF affects 1% of the female population. The age of onset can be as early as the teenage years, or can even exist from birth, but varies widely. If a girl never begins menstruation, it is called primary ovarian failure. The age of 40 was chosen as the cut-off point for a diagnosis of POF. By the age of 40, approximately one percent of women have POF.
The cause of POF is usually idiopathic. Some cases of POF are attributed to autoimmune disorders, others to genetic disorders such asTurner syndrome and Fragile X Syndrome. An Indian study showed a strong correlation between incidence of POF and certain variants in the inhibin alpha gene. Family history and ovarian or other pelvic surgery earlier in life are also implicated as risk factors for POF. There are two basic kinds of premature ovarian failure. Case 1) where there are few to no remaining follicles and case 2) where there are an abundant number of follicles. In the first situation the causes include genetic disorders, autoimmune damage, chemotherapy, radiation to the pelvic region, surgery, endometriosis and infection. In most cases the cause is unknown. In the second case one frequent cause is autoimmune ovarian disease which damages maturing follicles, but leaves the primordial follicles intact. Since the serum Antimullerian hormone (AMH) level is correlated with the number of remaining primordial follicles some researchers believe the above two phenotypes can be distinguished by measuring serum AMH levels.)
Infertility is the result of this condition, and is the most discussed problem resulting from it, but there are additional health implications of the problem, and studies are ongoing. For example, osteoporosis or decreased bone density affects almost all women with POF due to an insufficiency of estrogen. There is also an increased risk of heart disease, hypothyroidism in the form of Hashimoto’s disease, Addison’s disease, and other auto-immune disorders. Common causes include:
- Genetic disorders
- Autoimmune diseases
- Tuberculosis of the genital tract
- Smoking
- Radiation and/or chemotherapy
- Ovarian failure following hysterectomy
- Prolonged GnRH (Gonadatrophin Releasing Hormone) therapy
- Enzyme defects
- Resistant ovary
- Induction of multiple ovulation in infertility
Serum follicle-stimulating hormone (FSH) measurement alone can be used to diagnose the disease. Two FSH measurements with one-month interval have been a common practice. The anterior pituitary secretes FSH and LH at high levels due to the dysfunction of the ovaries and consequent low estrogen levels. Typical FSH in POF patients is over 40 mlU/ml (post-menopausal range). Women with POI have high LH levels, more evidence that the follicles are not functioning normal.
HRT improves sexual health and decreases the risks. Estrogens can be administered orally or transdermally. The appropriate dose for young women with ovarian failure has not been established in control studies. According to studies,administer doses twice as high as the recommended dose for HT for women who are postmenopausal (transdermal estradiol 100-150 mcg instead of 50 mcg daily, conjugated equine estrogens [CEE] 1.25 mg instead of 0.625 mg daily or oral estradiol 2-4 mg instead of 1 mg daily). Such doses usually achieve adequate estrogenization of the vaginal epithelium in young women with POI/POF and help maintain age-appropriate bone density.The estrogens can be administered continuously or cyclically (21 d on, 7 d off). Because no controlled studies compare the efficacy and safety of one method over another, the choice of therapy should come after consideration of the patient’s preference and physician’s experience. Progestins should be administered cyclically, 10-14 days each month, to prevent endometrial hyperplasia. Androgen replacement could be carefully considered for women who have persistent fatigue, low libido, and poor well being despite adequate estrogen replacement and when depression has been ruled out or adequately treated. This should be performed with great caution and for relatively short periods until more data are available.
A balanced and low-fat diet, regular exercise, and not smoking can help protect your bones and heart. Getting enough calcium and vitamin D may help slow bone loss. Infertility is a common complication of premature ovarian failure . DHEAS was useful to some extent (FSH level was decreased), it was decided to study the action of DHEA for a reasonable length of time and in a larger number of patients to confirm the effectiveness of this particular therapeutic regime .No intervention has been proven to increase the ovulation rate or restore fertility in patients with POI/POF.Gonadotropin therapy carries a theoretical risk of exacerbating autoimmune POI.The use of prednisone or dexamethasone in an attempt to restore ovarian function in suspected autoimmune ovarian failure is not indicated. Some women and their partners choose to pursue a pregnancy through in vitro fertilization using donor eggs. Embryo donation, in which frozen embryos are donated to the couple, is also often successful, and in general, less expensive.
Consultation with an endocrinologist may be indicated in some cases because of concerns of hypothyroidism or adrenal insufficiency. Patients with infertility due to POI/POF usually have a grief response after hearing the diagnosis. They may benefit from a baseline psychological evaluation and appropriate counseling. Genetic counseling may be needed in some cases.
