Vol. 16 •Issue 10
• Page 43
Stuck in Between
A Closer Look at Perimenopause
by Sarah Freeman, NP
For women, significant transitions occur at the start and end of reproductive life. Menarche occurs around age 12 and is preceded by several years of hormonal change. Menopause, which occurs around age 52, also features a prelude of hormonal disarray.
The transition period preceding menopause is referred to as perimenopause. It is characterized by menstrual irregularity followed by periods of amenorrhea. It typically features the start of menopausal symptoms such as hot flashes, sleep disturbances and vulvovaginal atrophy.
Multiple terms are used to describe the reproductive life cycle of women.1Poor understanding of these terms can lead to an incomplete approach to their clinical needs.
Women in perimenopause experience menstrual irregularity and varying levels of estrogen and follicle-stimulating hormone (FSH). This phase typically lasts 2 to 8 years.
Menopause signals passage from the reproductive stage to postmenopause.2It is defined as amenorrhea lasting more than 12 months.
Postmenopause is the period from menopause to death. It features low estrogen levels and high FSH levels.
Physiologic Changes
The perimenopausal period is associated with hormone fluctuations that manifest as changes in the menstrual cycle. Cycle length and amount of menstrual flow are commonly affected. Cycle length can begin to vary about 6 years prior to menopause. A recent study of 1,616 women ages 45 to 54 found that 58% of 45- and 46-year-olds and 100% of 53- and 54-year-olds had irregular cycles.3Numerous endocrine changes are associated with perimenopause, and they are directly linked to age. FSH levels start to change as early as a woman's 30s, and those changes increase in number and severity with age. A rise in FSH is associated with a decrease in total number of follicles.2FSH levels vary according to follicular development, leading to variable levels of luteinizing hormone (LH) and estradiol. The secretion of FSH is also under the influence of inhibin, a glycoprotein hormone produced by the ovarian granulosa cells. The decrease in ovarian follicles results in a reduction in inhibin that leads to FSH elevation.4
H is also elevated in perimenopause, but to a lesser degree than FSH. The amount of circulating estrogen varies widely, and these levels are associated with increased follicular stimulation due to elevated FSH. The wide swings in estrogen can cause hypoestrogenic and hyperestrogenic states, making treatment difficult.4Ovulation is unpredictable, leading to variations in progesterone levels. Hypoestrogenic periods become more frequent as menopause approaches.5,6 Remember that perimenopause is characterized by estrogen changes, not just low estrogen levels.
The changes in androgen levels associated with perimenopause are the subject of clinical controversy. Androgens are primarily produced in the ovary by interstitial cells. The other major source of androgens is the adrenal gland. Compared with a menstruating woman, the perimenopausal woman does not have a significantly different level of testosterone. But testosterone levels are noticeably lower in a postmenopausal woman.7The lack of definitive changes in testosterone levels among perimenopausal women has made it difficult to determine the role of testosterone in the treatment of sexual dysfunction in premenopausal women.
Signs and Symptoms
The symptoms that may affect a woman's quality of life during perimenopause are quite varied (Table 1). More than 80% of perimenopausal women report experiencing vasomotor symptoms.8 The most common one is hot flashes. These apparently occur when estrogen changes disrupt the balance between norepinephrine and dopamine, causing vasomotor instability.9Rule out alternate causes of vasomotor symptoms before reaching a diagnosis of perimenopause. Many conditions can mimic vasomotor symptom (Table 2).
Mood and cognitive changes are also common during perimenopause, possibly the result of hormonal shifts. Memory problems and emotional instability may occur.10These changes, in combination with significant life changes such as children moving out, altered spousal relationships and perceived loss of beauty increase a woman's risk for depression.11
Psychosocial symptoms may affect quality of life more noticeably than physical symptoms. In a study of 214 perimenopausal women, participants did not cite vasomotor symptoms as the most significant cause of decreased quality of life. Instead, most women reported psychosocial symptoms such as emotional upheaval, anxiety and memory loss as most distressing. Using the Women's Heath Assessment Scale and the Quality of Life Scale, researchers noted a slight but significant decrease in quality of life among the women.12
During the perimenopausal period, patients may complain of changes in sexuality. The most common are vulvovaginal atrophy and decreased libido. Vulvovaginal atrophy is related to decreasing estrogen levels. It may manifest as itching, dryness and irritation. Naturally occurring vaginal lubrication also declines with the gradual depletion of estrogen. Intercourse can become painful. About 75% of perimenopausal women experience one or more of these changes to sexual functioning.13Decreased libido is also common during perimenopause. The precise mechanism of action for this symptom is poorly understood. One study found that 86% of perimenopausal women reported loss of interest in sex as well as decreased responsiveness.10Testosterone is the hormone thought to play the biggest role in libido, and it is unchanged during perimenopause.7The presence of other symptoms, such as depression, vaginal atrophy, dyspareunia, anxiety and relationship difficulties, may play a role in libido change.
Perimenopause and Chronic Disease
The risk for chronic disease increases with age. Be attentive to the prevention and early detection of chronic diseases that particularly affect women. While the greatest bone loss occurs in the first 5 years after menstruation ceases, perimenopause can also be a time of bone degeneration. As estrogen levels decline, normal bone remodeling is altered, and more bone resorption than bone formation occurs. Patients at high risk for osteoporosis (Table 3) may need to be screened for bone mineral density at this time, not after menopause occurs. All women require education about how to preserve bone mass with diet, exercise, calcium and vitamin D.
Cardiovascular disease (CVD) is the leading cause of death in women, and its incidence increases with age.8 As estrogen levels decrease and lipid profiles become more atherogenic, the risk for CVD rises. Research does not show that estrogen replacement is cardioprotective in older women.14,15Naturally occurring estrogen provides a number of cardioprotective benefits, including favorable effects on lipoprotein profile.16As women age and estrogen levels decline, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and total cholesterol all increase.
Hypertension and diabetes are two of the most common chronic disorders diagnosed during the perimenopausal transition.17,18Each increases a woman's risk for CVD. Along with control of any chronic disease, lifestyle modifications are important in the prevention of CVD. To identify the presence of or risk for disease, screen all midlife women according to published guidelines (Table 4).19-23
Diagnosis
The major diagnostic tools for perimenopause are a complete history and a complete physical examination. Measurements of FSH and estradiol have not proven useful because perimenopause can cause hypo- and hyperestrogenism.4,8,17 aboratory testing may be an unnecessary expense; the patient's symptoms should guide the course of clinical care.
Management
The clinical goals for managing perimenopausal symptoms are to provide relief and to screen for health problems. Treatment should focus on prevention and optimization of good health. This should include comprehensive screening for physical and psychosocial problems. Lifestyle counseling to reduce the risk and incidence of chronic disease is an essential component of care.18
Patients in perimenopause need to understand the effects of lifestyle on health and illness. A nutritious diet is essential to maintaining a recommended body weight and promoting overall health. A low-fat diet rich in fruits, vegetables and whole grains is necessary to reduce the risk for CVD, hypertension and diabetes. Adequate calcium is necessary for the promotion of bone health.24Women should ingest at least 1,200 mg/day of elemental calcium in food sources (dairy, tofu, broccoli, salmon, sardines, etc.) and supplements. Vitamin D is necessary for the body to utilize calcium.25Foods such as vitamin D-fortified milk and bread can help women obtain adequate levels of this nutrient.
Although exposure to the sun can provide vitamin D, sunscreens block this benefit. Daily supplementation of 400 IU to 800 IU of vitamin D is often necessary.24Regular exercise is an important preventive strategy during perimenopause and beyond. Exercise routines should incorporate cardiovascular activity, weight-bearing activity and strength training. In general, women should exercise 5 to 7 days a week at moderate intensity. Regular exercise can help maintain a healthy body weight, elevate HDL cholesterol, increase insulin sensitivity and promote bone mass.
Smoking is associated with numerous long-term health problems and can lead to early menopause.25Encourage cessation by all patients who smoke. Provide assistance in the form of medication and referral to a smoking cessation program, if needed. Screen patients for drug and alcohol problems, and provide treatment or referral.
Although fertility decreases with age, women are capable of becoming pregnant until menopause.26,27Perimenopausal women who are healthy and do not smoke can use most methods of contraception (Table 5).
Certain contraceptive choices have the added benefit of managing the symptoms associated with this stage of life (Table 6).27Just as with younger women, discuss all contraceptive choices and perform a thorough history and physical before prescribing or recommending birth control. Choice of contraception can affect perimenopausal symptoms.
Menstrual Irregularities
Patients who experience abnormal bleeding require a detailed history as part of the overall assessment. Collect data about the length, character, duration and amount of the bleeding episodes as well as details about their frequency.
Focus laboratory testing on ruling out other diagnoses. Order a complete blood count to assess for anemia, along with pregnancy testing, prolactin levels and thyroid-stimulating hormone levels. Depending on the history and symptoms, coagulation studies may be needed.
The workup for any perimenopausal woman with abnormal bleeding should be aimed at ruling out endometrial carcinoma. Some of the clinical risk factors for endometrial hyperplasia and cancer are obesity, age older than 45, history of infertility, family history of colon cancer and nulliparity.
Order endometrial sampling to rule out carcinoma. Medical management for hyperplasia without atypia consists of cyclic or noncylic hormones (Tables 7 and 8). Prescribe estrogen with progesterone or progesterone alone. Hormonal contraception can decrease irregular bleeding, and progesterone protects the endometrium.11,28
Vasomotor Symptoms
Although data support the use of estrogen and progestins for vasomotor symptoms in postmenopause, less information is available about their use in perimenopause.
Because of the varying levels of estrogen in perimenopause, hormone therapy prescribed as "replacement" therapy may not provide relief. In one observational study, less than 50% of patients who received hormones prescribed in this manner experienced complete relief from symptoms.29
emember that hormone therapy is designed to treat symptoms of perimenopause or menopause and will not prevent pregnancy. A better choice might be combined hormonal contraception. In doses and formulations designed for contraception, hormones will shut down the function of the ovary and provide estrogen and progesterone to relieve symptoms.11
Vaginal atrophy can be treated with vaginal estrogen products. The degree of systemic absorption is small, and it does not contribute to variations in hormone levels. Low-dose vaginal estrogen is effective in relieving unpleasant vaginal symptoms and may be even more effective than systemic estrogen.30
The use of testosterone to increase libido is controversial; it is a more common intervention after a woman reaches menopause. Testosterone replacement in perimenopausal women is challenging because optimal dosing has not been studied in this population. If androgens are elevated above physiologic levels, women may demonstrate signs of androgen excess.31
Putting It Into Practice
Management of the perimenopausal woman can be complex. The primary goals of treatment are to relieve bothersome symptoms, to promote health and to prevent disease. During perimenopause, women are at increased risk for many chronic diseases. Be aware of this possibility, and tailor care to meet the needs of each patient.
References
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2. Speroff L, et al. Clinical Gynecologic Endocrinology and Infertility. 6thed. New York, N.Y.: Lippincott Williams and Wilkins; 1999.
3. Astrup K, et al. Menstrual bleeding patterns in pre- and perimenstrual women: a population based prospective diary study. Acta Obstet Gynecol Scand. 2004;83(2):192-202.
4. Santoro N, et al. Characterization of reproductive hormonal dynamics in the perimenopause. J Clin Endocrinol Metab. 1996;81(4):1495-1501.
5. Snyder TE. Perimenopause In: Bieder EJ, et al. Clinical Gynecology. Philadelphia, Pa.: Churchill Livingstone Elsevier; 2006.
6. Prior JC. The ageing female reproductive axis II: ovulatory changes with perimenopause. Novartis Found Symp. 2002;242:172-188.
7. Burger HG, et al. The endocrinology of the menopausal transition: a cross-sectional study of a population-based sample. J Clin Endocrinol Metab. 1995;80(12):3537-3545.
8. Frackiewicz EJ, Cutler NR. Women's health care during perimenopause. J Am Pharm Assoc. 2000;40(2):800-811.
9. Cook MJ. Perimenopause: an opportunity for health promotion. J Obstet Gynecol Neonatal Nurs. 1993;22(3):233-228.
10. Condon MC. Women's Health. Body, Mind, and Spirit: An Integrated Approach to Wellness and Illness. Prentice Hall, N.J.: Prentice Hall; 2004.
11. Kaunitz AM. Gynecologic problems in the perimenopause: evaluation and treatment. Obstet Gynecol Clin North Am. 2002;29(3):455-473.
12. Li S, et al. Perimenopause and the quality of life. Clin Nurs Res. 2000;9(1):6-23.
13. Nachtigall LE. The symptoms of perimenopause. Clin Obstet Gynecol. 1998;41(4):921-927.
14. Hsia J, et al. Conjugated equine estrogen and coronary heart disease: the Women's Health Initiative. Arch Int Med. 2006;166(3):357-365.
15. Grady D, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen Progestin Replacement Study follow-up (HERS II). JAMA. 2002;288(1):49-57.
16. Mendelsohn ME, Karas RH. The protective effects of estrogen on the cardiovascular system. N Engl J Med. 1999;340(23):1801-1811.
17. Sulak PJ. The perimenopause: a critical time in a woman's life. Int J Fertil Menopausal Stud. 1996;41(2):85-89.
18. Clinical challenges of perimenopause. Consensus opinion of the North American Menopause Society. Menopause. 2000;7(1):5-13.
19. American College of Obstetricians and Gynecologists. Health maintenance for perimenopausal women. ACOG Technical Bulletin Number 210. Int J Gynaecol Obstet. 1995;51(2):171-181.
20. Speroff L, et al. Symposium: preventive care during the transitional years. Contemporary OB/GYN. 1996;41(1):95-100.
21. American Cancer Society Guidelines. Colorectal cancer screening resource kit. Available at http://www.cancer.org/docroot/PRO/PRO_4_ColonMD.asp. Accessed July 2, 2008.
22. American Diabetes Association. Clinical practice recommendation 2005. Diabetes Care. 2005;28:S4-S36.
23. Laderson PW, et al. American Thyroid Association guidelines for detection of thyroid dysfunction. Arch Intern Med. 2000;160(11):1573-1575.
24. National Osteoporosis Foundation. Osteoporosis: impact and overview. Available at http://www.nof.org/professionals/NOF_Clinicians_Guide.pdf. Accessed July 2, 2008.
25. Lichtman, R. Perimenopausal and postmenopausal hormone replacement therapy part 2: hormonal regimens and complementary and alternative therapies. J Nurse Midwifery. 1996;41(3):195-210.
26. Klein J, Sauer MV. Assessing fertility in women of advanced reproductive age. Am J Obstet Gynecol. 2001;185(3):758-770.
27. Kailas NA. Contraception during perimenopause. Eur J Contracept Reprod Health Care. 2005;10(1):19-25.
28. Farquhar CM, et al. An evaluation of risk factor for endometrial hyperphasia in premenopausal women with abnormal uterine bleeding. Am J Obstet Gynecol. 1999;81(3):525-529.
29. Shulman LP, Harari D. Low dose transdermal estradiol for symptomatic perimenopause. Menopause. 2004;11(1):34-39.
30. Kaunitz AM. Sexual pain and genital atrophy: breaking down barriers to recognition and treatment. Menopause Mgt. 2001;10(6):22-32.
31. Litchman R. Perimenopausal and postmenopausal hormone replacement therapy: Part 1. An update of the literature on benefits and risk. J Nurse Midwifery. 1996;41(3):228-229.
Sarah Freeman is a women's health nurse practitioner who is a clinical professor of nursing at Emory University in Atlanta.
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