The North American Menopause Society (NAMS) states that menopause should be regarded as a natural biological process and not a specific disease entity.1 The menopausal transition is a process that can last several years and is often associated with numerous undesirable manifestations.
The median age of onset of menopause in the United States is 51 years. Prior to menopause is the transition period known as perimenopause.2 Perimenopause is characterized by irregular uterine bleeding due to oligo/anovulation and is often marked by the onset of menopausal symptoms. Menopause is defined as the permanent cessation of menses secondary to the loss of ovarian follicular activity. It is characterized by a change in circulating hormone concentrations, such as a more than 10-fold increase in follicle-stimulating hormone (FSH) and a more than 4-fold increase in luteinizing hormone levels. Menopause is often diagnosed retrospectively after 12 months without menstrual periods in the absence of any other cause for amenorrhea and by the presence of vasomotor symptoms such as hot flashes. A thorough medical history, physical examination, and FSH serum level should confirm the diagnosis.3 The clinical presentation of menopause may include vasomotor symptoms, genitourinary atrophy, nausea, headache, dizziness, sleep disturbances, mood changes, and/or sexual dysfunction.4
Hormone therapy (HT) options for menopausal symptoms include estrogen therapy (ET) and combined estrogen plus progestins. Alternative therapies for patients in which HT is contraindicated are also available.
Although HT is currently the most effective treatment for menopausal symptoms, the Women?s Health Initiative, a National Institutes of Health?sponsored randomized clinical trial, found that there was an increased risk of cardiovascular disease and breast cancer in some patients associated with combined conjugated equine estrogen plus medroxyprogesterone acetate.5,6 Since the publication of this study, concerns regarding the safety and long-term consequences of HT have made its use controversial. Despite this, both the American College of Obstetricians and Gynecologists and NAMS have issued statements indicating that the short-term use of HT may still be appropriate for the relief of vasomotor symptoms in certain patients.1,7 Health care providers should keep in mind that the decision to start or continue HT must be individualized, based on a complete clinical assessment, and consider the benefits, risks, and alternatives available to each woman. Absolute contraindications to HT include undiagnosed vaginal bleeding, pregnancy, estrogen-dependent malignancies, known or suspected breast cancer, and active thromboembolic disorders. Common adverse effects include nausea, hypertriglyceridemia, edema, breast tenderness, mood swings, and acne.3
HT is indicated for the treatment of moderate-to-severe vasomotor symptoms associated with menopause and moderate-to-severe vulvovaginal atrophy associated with the menopause. These symptoms are described as "intolerable" by 10% to 20% of the women who experience them and can severely impact a woman?s quality of life. Hot flashes are often described as a sensation of warmth, frequently accompanied by skin flushing and perspiration, and may be followed by a chill. These may occur in women of any age who experience acute estrogen withdrawal and can last more than 5 years in up to 75% of affected women. Urogenital symptoms, such as vaginal dryness, also detract from a woman?s quality of life and cause many to seek treatment.8
Studies have shown ET to be effective in the treatment of moderate-to-severe vasomotor menopausal symptoms. Systemic estrogen therapy is also associated with several other benefits, including the prevention of postmenopausal osteoporosis. Estrogen monotherapy should be restricted to patients who have undergone a hysterectomy due to the risk of endometrial hyperplasia. Women should be given the lowest estrogen dose necessary to help alleviate symptoms, and the length of therapy should be limited to the shortest possible duration. Commonly used systemic estrogen formulations include conjugated equine estrogens, micronized 17?-estradiol, and ethinyl estradiol.9
The primary menopause-related indication for progestin use is endometrial protection from unopposed estrogen therapy. Unopposed estrogen therapy in women with an intact uterus significantly increases the risk for endometrial cancer. Progestins can be prescribed continuously or cyclically. In some cyclic regimens, estrogen is administered daily and a progestin is added for 14 days each month. Some commonly used progestins include medroxyprogesterone acetate (MPA), micronized progesterone, norethindrone, and levonorgestrel.9,10 Side effects tend to vary among these agents but may include mood swings, bloating, fluid retention, and sleep disturbances.3
A novel progestin, drospirenone, is currently being used in combination with estradiol for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. Drospirenone is a spironolactone analog with antialdosterone and antimineralocorticoid activity. It has a pharmacologic profile that is more similar to endogenous progesterone than that of other available progestins. Drospirenone is currently used in oral contraceptives and can also be found in the combination HT product Angeliq (drospirenone/estradiol).12
Angeliq contains 1 mg of estradiol with 0.5 mg of drospirenone and is indicated for the treatment of moderate-to-severe vasomotor symptoms as well as the treatment of moderate-to-severe symptoms of vulvar and vaginal atrophy associated with menopause. This combination product is effective in reducing these symptoms without causing an increase in the incidence of endometrial hyperplasia at 1 year.
Angeliq may be a treatment option for the effective management of menopausal symptoms in appropriate women.
1. Estrogen and progestogen use in peri- and postmenopausal women: March 2007 position statement of the North American Menopause Society. Menopause. 2007;14:168-182.
2. Blake J. Menopause: evidence-based practice. Best Pract Res Clin Obstet Gynaecol. 2006;20(6):799-839.
3. Kalantaridou S, Davis SR, Calis KA. Hormone therapy in women. In: Dipiro JT, Talbert RC, Yee GC, et al. 6th ed. Pharmacotherapy: A Pathophysiologic Approach. New York, NY: McGraw-Hill; 2005.
4. Santoro N. The menopausal transition. Am J Med. 2005;118(suppl 12B):8-13.
5. Manson, JE, Hsia J, Johnson KC, et al: Women?s Health Initiative Investigators. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349: 523-524.
6. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefit of estrogen plus progestin in healthy postmenopausal women; principal results from Women?s Health Initiative randomized control trial. JAMA. 2002;288:321-333.
7. North American Menopause Society. Treatment of menopause-associated vasomotor symptoms: position statement of the North American Menopause Society. Menopause. 2004;11(1):11-33.
8. American College of Obstetricians and Gynecologists. Vasomotor symptoms in hormone therapy. Obstet Gynecol. 2004;104(suppl):106S-117S.
9. AACE Menopause Guidelines Revision Task Force. American Association of Clinical Endocrinologists medical guidelines for clinical practice for the diagnosis and treatment of menopause. Endocr Pract. 2006;12(3):315-337.
10. Brigham and Women?s Hospital. Menopause: A guide to management. Boston, Mass. Brigham and Women?s Hospital; 2005.
11. Foidart JM. Added benefits of drospirenone for compliance. Climacteric. 2005 Oct(8 suppl 3):28-34.
12. Archer DF. Drospirenone and estradiol: a new option for menopausal women. Climacteric. 2007 Feb(10 suppl 1):3-10.
One study linked multiple pregnancies to an increased risk of developing atrial fibrillation later in life, and another investigated the association between premature delivery and cardiovascular disease.
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