- Author: Kenneth M Bielak, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG more...
For primary amenorrhea, hormone therapy, consisting of an estrogen and a progestin, is recommended for women with estrogen deficiency. Girls with primary amenorrhea typically do not have symptoms of estrogen deficiency. However, with inadequate estrogen exposure over time, these patients are at increased risk for developing osteoporosis and possibly other health issues.
Young women in whom secondary sex characteristics have failed to develop fully should be exposed initially to very low doses of estrogen in an attempt to mimic the gradual pubertal maturation process. A typical regimen consists of an estrogen with a dosage equivalent to 25 mcg/day of transdermal estradiol (approximately 0.3 mg of conjugated equine estrogen) given unopposed (ie, no progesterone) daily for 6 months with incremental dose increases at 6-month intervals until the required maintenance dose is achieved.
Gradual dose escalation allows time to balance estrogen supplementation with need to grow in height, develop secondary sexual characters, and often results in optimal breast development. It also allows time for the young woman to adjust psychologically to her physical maturation.
Cyclic progesterone therapy, given 12-14 days per month, should be instituted once vaginal bleeding begins.
Parenteral estrogen (transdermal or vaginal) is the preferred route of administration because it avoids first-pass liver metabolism. Moreover, it is less likely to increase sex hormone–binding globulin (SHBG) and has little or no effect on circulating lipids, coagulation parameters, or C-reactive protein. However, no long-term controlled studies are available to compare the efficacy and safety of one method over another. Therefore, the choice of therapy should follow consideration of the patient's preferences and the physician's experience.
The role of androgen replacement is unclear at this time and is the subject of ongoing investigation.
For secondary amenorrhea, dopamine agonists are the only medical therapy specifically approved to reverse an underlying pathology that leads to amenorrhea. In most cases, dopamine agonists effectively reduce hyperprolactinemia.
Gonadotropin therapy or pulsatile gonadotropin-releasing hormone (GnRH) therapy is indicated in women who desire fertility yet remain anovulatory because of an unresolved hypothalamic/pituitary disorder. GnRH pump therapy is available in Europe but not in the United States.
Once the diagnosis is established, for some women with oligomenorrhea or amenorrhea who do not wish to become pregnant, oral contraceptives may be a good choice to restore menstrual cyclicity and provide estrogen replacement. The absence of pregnancy should be documented before oral contraceptive therapy is begun.
In patients with amenorrhea or oligomenorrhea withdrawal bleeding should be induced with an injection of progesterone or the administration of 5-10 mg of medroxyprogesterone for 10 days.
Hormone therapy, consisting of an estrogen and a progestin, is needed for women in whom estrogen deficiency remains because ovarian function cannot be restored. The role of androgen replacement is unclear at this time and is the subject of ongoing investigation.
Estrogens are administered transdermally, transvaginally, or orally. The appropriate dose for young women with ovarian failure or secondary amenorrhea has not been established. The authors recommend full replacement doses for young women. Generally, this is approximately twice as high as doses recommended for hormone therapy in normally postmenopausal women.
The authors prefer to administer estradiol by skin patch (100-mcg transdermal estradiol patch). This avoids the first-pass effect of oral estrogen on the liver. No controlled studies are available to compare the efficacy and safety of one method over another. Therefore, the choice of therapy should follow consideration of the patient's preferences and the physician's experience.
Estradiol increases synthesis of DNA, RNA, and many proteins in target tissues. Transdermal patch available as Alora (0.05, 0.075, and 0.1 mg/d, applied twice weekly), Climara (0.025, 0.05, 0.075, and 0.1 mg/d, applied once weekly), Esclim (0.025, 0.0375, 0.05, 0.075, 0.1 mg/d, applied twice weekly), and Vivelle-dot (0.037, 0.05, 0.075, 0.1 mg/d, applied twice weekly). If transdermal patch is not tolerated, oral form may be used.
Use in patients who refuse or do not tolerate other forms of estrogen. Use oral estrogen to achieve adequate estrogenization of vaginal epithelium in young women and adequately maintain bone density.
Progestins stop endometrial cell proliferation, allowing organized sloughing of cells after withdrawal. No long-term controlled studies compare efficacy of medroxyprogesterone with oral progesterone in protecting the endometrium from neoplasia at the doses of estrogen generally required for replacement in young women. The authors recommend use medroxyprogesterone as first-line therapy because of longer-term clinical experience with this agent.
Administer cyclically 12 d/mo to prevent endometrial hyperplasia that unopposed estrogen may cause. In young women, regular withdrawal bleeding is preferable because even young women with premature ovarian failure have a 5-10% chance of spontaneous pregnancy (unlike postmenopausal women). If an expected withdrawal bleeding is absent, perform a pregnancy test (and a timely diagnosis of pregnancy will not be missed). Other causes of amenorrhea may also remit spontaneously and result in an unexpected pregnancy.
This agent is used to prevent endometrial hyperplasia
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