MEDICAL TREATMENT :
Medical treatment of patients with POF should address the following aspects: ovarian hormone replacement, restoration of fertility, and psychological well being of the patient. For women with secondary ovarian failure, the treatment required to restore ovarian function depends on the specific etiology.
Management of premature ovarian failure
Inform
Discuss the test results on a special visit (not by phone).
The diagnosis of POF can be particularly traumatic for young women.
Use of appropriate terminology is important (use of premature ovarian failure or insufficiency is preferred instead of premature menopause or early menopause).
Explain the nature of the disease and advise the patient of sources of information and support.
Counsel
The ovary is not only a reproductive organ but also is a source of important hormones that help maintain strong bones. Adequate replacement of these missing hormones, a healthy lifestyle, and a diet rich in calcium are essential. DEXA bone scan every 2 years may be needed.
POF is not menopause. Spontaneous ovarian activity and pregnancies are possible.
Allow the patient enough time to accept the diagnosis. Discuss fertility plans later, after the patient has come to terms with her condition.
No proven therapies exist to restore fertility, and an experimental treatment should be performed only under a review boardβapproved research protocol.
Currently available options to resolve infertility include change of plans, adoption, and ovum donation.
Replace deficient hormones
Cyclic/continuous oral/transdermal estrogen and cyclic oral progestin are needed.
Full replacement dose is needed to alleviate symptoms and maintain age-appropriate bone density.
Follow-up
Adequacy of hormone replacement therapy (HRT) should be followed yearly.
TSH and adrenal antibodies (expert opinion) should be followed yearly.
ACTH stimulation test should be performed yearly if the adrenal antibodies are positive.
DEXA bone density scan should be performed as needed.
Hormone replacement therapy: All women with premature ovarian failure should receive HRT with estrogens and progestins to relieve the symptoms of estrogen deficiency, to maintain bone density, and to reduce the risk of cardiovascular diseases. Some women may need HRT even before amenorrhea develops to alleviate menopausal symptoms.
Estrogens
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 the authors' clinical judgment, administer doses twice as high as the recommended dose for HRT for women who are postmenopausal (conjugated equine estrogens [CEE] 1.25 mg instead of 0.65 mg daily, oral estradiol 2-4 mg instead of 1 mg daily, and transdermal estradiol 100-150 mcg instead of 50 mcg daily). Such doses usually achieve adequate estrogenization of the vaginal epithelium in young women with POF and probably help to 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.
Estrogen replacement therapy does not prevent ovulation and conception in these patients, and they should be informed that they must obtain a prompt pregnancy test if menstrual bleeding fails to appear when expected.
Oral contraceptives provide more sex steroid than is required for replacement, and the authors advise against this approach. Furthermore, owing to the elevated gonadotropin levels, oral contraceptives may not be effective in preventing pregnancy in women with premature ovarian failure.
Progestins
Progestins should be administered cyclically, 10-14 days each month, to prevent endometrial hyperplasia that unopposed estrogen may cause. Young women with POF have a 5-10% chance of spontaneous pregnancy (unlike women who are postmenopausal). If an expected withdrawal bleeding is missing, a pregnancy test should be performed and a diagnosis of pregnancy should not be delayed.
The recommended regimens include medroxyprogesterone 10 mg daily for 10-12 days each month or micronized progesterone 200 mg daily for 10-12 days each month.
Androgens
Women with ovarian failure have lower levels of free testosterone compared to normally ovulating age-matched controls, but only a small percentage have levels below the lower limit of normal.
Clinical trials are underway to determine whether testosterone replacement should be a part of the standard therapy for young women with ovarian failure. Additional information can be obtained by calling the Section on Women's Health Research at the US National Institute of Child Health and Human Development, Bethesda, Maryland at (877) 206-0911.
Until results from these trials are available, androgen replacement could be 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.
Available medications include oral methyl testosterone 1.25-2.5 mg/d, injectable testosterone esters 50 mg every 6 weeks intramuscularly, and subcutaneous testosterone pellet implants 50 mg every 3-6 months. A testosterone transdermal patch, designed to deliver 150 mcg per day, currently is undergoing a clinical trial.
Restoration of fertility: No intervention has been proven to increase the ovulation rate or restore fertility in patients with POF.
Gonadotropin therapy carries a theoretical risk of exacerbating autoimmune premature ovarian failure.
The use of prednisone or dexamethasone in an attempt to restore ovarian function in suspected autoimmune ovarian failure is not indicated clinically. Use of these agents carries a risk of osteonecrosis. Their use in patients with premature ovarian failure should be confined to studies approved by an institutional review board.
Unproven treatments to restore fertility should be avoided because they have the potential of interfering with the development of a spontaneous pregnancy.
Patients with POF can have successful pregnancy with a donor egg. A decision to proceed with such a procedure should be made after a fair discussion of different options. The age of the patient is of less importance than the age of the egg donor.
Other possibilities include adoption or change of life plans.
For women with secondary ovarian failure, the treatment required to restore fertility depends on the specific etiology.
Surgical Care: Ovarian biopsy is not clinically indicated in women with ovarian failure, but surgical procedures should be performed in women with secondary ovarian failure as indicated when hypothalamic or pituitary lesions are identified.
DRUG TREATMENT :
1. ESTROGENS - Used to achieve adequate estrogenization of vaginal epithelium in young women and to maintain bone density
- ESTRADIOLTRANSDERMAL SYSTEM
- CONJUGATED EQUINE ESTROGENS ( PREMARIN )
2. PROGESTINS : When administered orally in the recommended doses to women adequately exposed to exogenous or endogenous estrogen, they transform the proliferative endometrium into a secretory one.
- MEDROXYPROGESTERONE : Derivative of progesterone. Androgenic and anabolic effects have been noted, but apparently is devoid of significant estrogenic activity. Parenterally administered dosage form inhibits gonadotropin production, which, in turn, prevents follicular maturation and ovulation. Available data indicate that this does not occur when the usually recommended PO dose is administered qd.
- PROGESTERONE : Used to prevent endometrial hyperplasia in women with a uterus who are receiving estrogen replacement therapy.
3. ANDROGENS : Responsible for normal growth and the development and maintenance of secondary sex characteristics in males. In addition, androgens have exhibited metabolic activity and may cause retention of nitrogen, sodium, potassium, and phosphorus and decrease urinary excretion of calcium. In the presence of sufficient caloric and protein intake, they will improve nitrogen balance. Androgens also have been reported to stimulate production of RBCs through the enhancement of erythropoietin production. Also increase muscle mass, improve muscle strength, and increase libido.
- METHYLTESTOSTERONE
- TESTOSTERONE ENANTHATE