Ovarian Insufficiency Treatment & Management: Medical Care, Surgical Care, Consultations

Medical Care

Medical treatment of patients with POI/POF should address the following aspects: ovarian hormone replacement, restoration of fertility, and psychological well being of the patient. (For management of secondary ovarian insufficiency, refer to articles discussing the specific causes of it, such as anorexia nervosa, hypothalamic amenorrhea, prolactinoma.)

Management of primary ovarian insufficiency

• Inform
  • Discuss the test results on a special visit (not by phone).
  • The diagnosis of POI/POF can be particularly traumatic for young women.
  • Use of appropriate terminology is important (use of POI 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 is also 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.
  • POI/POF is not menopause. Spontaneous ovarian activity and pregnancies are possible.
  • Allow the patient enough time to accept the diagnosis. Family planning decisions are best made after the patient has had some time to come to terms with her condition.
  • No proven therapies exist to restore fertility; experimental treatment should be performed only under a review board–approved research protocol.
  • Currently available options to resolve infertility include change of family building plans, such as adoption, ovum donation, or embryo donation.
• Hormone therapy (HT)
  • All women with POI/POF should receive cyclical HT with estrogens and progestins to relieve the symptoms of estrogen deficiency and to maintain bone density.
  • A few women may need HT 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 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.
  • Estrogen therapy (ET) does not prevent ovulation and conception in these patients; in fact, it may improve the chance of pregnancy by theoretically lowering the LH level to normal range and preventing premature luteinization of the remaining follicles.Patients 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 POI.
• Progestins
  • Progestins should be administered cyclically, 10-14 days each month, to prevent endometrial hyperplasia that unopposed estrogen may cause. Young women with POI/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 with normally ovulating age-matched controls, but only 13% have levels below the lower limit of normal.
  • 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.
  • Available medications include oral methyltestosterone 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.
• Restoration of fertility: 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 clinically.
• Use of these agents carries a risk of osteonecrosis. Their use in patients with POI 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 POI/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 embryo adoption, adoption, or change of life plans.

Surgical Care

Ovarian biopsy is not clinically indicated in women with ovarian failure.

Consultations

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.

Referral for eye care is indicted in women with symptoms of dry eye.

Diet

Patients with ovarian failure should consume 1200-1500 mg of elemental calcium per day in their diet. If this is not feasible, calcium supplementation is appropriate. An adequate intake of vitamin D is also important.

Activity

Women with POI/POF should be encouraged to engage in weight-bearing exercises for 30 minutes per day, at least 3 days per week, to improve muscle strength and maintain bone mass. Participation in outdoor sports is strongly recommended.

Medication

Vaishali Popat, MD, MPH Clinical Investigator, Intramural Research Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Vaishali Popat, MD, MPH is a member of the following medical societies: American College of Physicians, Endocrine Society

Coauthor(s)

Lawrence M Nelson, MD, MBA Head of Integrative Reproductive Medicine Group, Intramural Research Program on Reproductive and Adult Endocrinology, National Institutes of Child Health and Human Development, National Institutes of Health

Lawrence M Nelson, MD, MBA is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Endocrine Society, Society for Experimental Biology and Medicine

Karim Anton Calis, PharmD, MPH FASHP, FCCP, Clinical Professor, Medical College of Virginia, Virginia Commonwealth University; Clinical Professor, University of Maryland; Clinical Investigator, Office of the Clinical Director, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health

Karim Anton Calis, PharmD, MPH is a member of the following medical societies: American College of Clinical Pharmacy, American Society of Health-System Pharmacists, Endocrine Society

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

A David Barnes, MD, MPH, PhD, FACOG Consulting Staff, Department of Obstetrics and Gynecology, Mammoth Hospital (Mammoth Lakes, CA), Pioneer Valley Hospital (Salt Lake City, UT), Warren General Hospital (Warren, PA), and Mountain West Hospital (Tooele, UT)

A David Barnes, MD, MPH, PhD, FACOG is a member of the following medical societies: American College of Forensic Examiners Institute, American College of Obstetricians and Gynecologists, Association of Military Surgeons of the US, American Medical Association, Utah Medical Association

Chief Editor

Richard Scott Lucidi, MD, FACOG Associate Professor of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Virginia Commonwealth University School of Medicine

Richard Scott Lucidi, MD, FACOG is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine

Robert K Zurawin, MD Associate Professor, Chief, Section of Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, Baylor College of Medicine

Robert K Zurawin, MD is a member of the following medical societies: American College of Obstetricians and Gynecologists, American Society for Reproductive Medicine, Association of Professors of Gynecology and Obstetrics, Central Association of Obstetricians and Gynecologists, Society of Laparoendoscopic Surgeons, Texas Medical Association, AAGL, Harris County Medical Society, North American Society for Pediatric and Adolescent Gynecology

Disclosure: Received consulting fee from Ethicon for consulting; Received consulting fee from Bayer for consulting; Received consulting fee from Hologic for consulting.

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• Table. Clinical Situations of Primary Ovarian Insufficiency and Premature Ovarian Failure

Table. Clinical Situations of Primary Ovarian Insufficiency and Premature Ovarian Failure

Ovarian Clinical Situation	Menses	Gonadotropins	Fertility
Occult insufficiency	Normal	Normal	Reduced
Biochemical insufficiency	Abnormal	Elevated	Reduced
Overt insufficiency	Abnormal	Elevated	Reduced
Premature ovarian failure	Absent	Elevated	Zero