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C L I N I C A L U P D A T E
menopause Management, Part 1:
perimenopausal
tr ansition and
early menopause
What is the difference between
menopause and perimenopause?
By Regula Burki, M.D.
menopause as the “permanent cessation of menstruation resulting from the loss of ovarian follicular activity.” The mean age of natural menopause, or the last period, is about 51 years, with a range between 45 and 55, and has remained relatively stable throughout re-corded history, as opposed to the age of menar-che, which has steadily decreased over thecourse of the 20th century.
Symptoms, such as hot flashes,
ovarian failure,” is cessation of menses beforeage 40 and occurs in one to eight percent ofwomen. Artificial menopause is caused by sur- night sweats, and vaginal
gical removal of the ovaries, radiation, orchemotherapy. Smoking, history of pelvicsurgery, and living at a high altitude correlate dryness, may be experienced
with early menopause, while age of menarcheand age of maternal menopause do not.
Perimenopause is the time in a woman’s life years before the actual
that leads up to menopause. Also referred to as“perimenopausal transition,” it is marked bysigns and symptoms of declining and erratic menopause.
ovarian function and lasts from four to fiveyears. The menstrual irregularities typical of 164 CORTLANDT FORUM
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the perimenopausal transition years are related to Both thyroid-stimulating hormone and prolactin changes in ovulation and progesterone production.
levels should be determined in most perimenopausal Fluctuating estrogen levels result in a variety of symp- women presenting with menstrual irregularities, toms: Hot flashes, night sweats, symptoms of urogen- especially in the absence of other typical peri- ital atrophy, emotional instability, and irritability are menopausal symptoms. Hypothyroidism with result- due to low estrogen levels, while mastodynia and ing irregular periods is quite common in this age fibroid growth are triggered by higher-than-normal group, and one would not want to miss the occasion- What blood tests can confirm the diagnosis?
What causes hot flashes?
Women in their 40s often demand to “have their Vasomotor symptoms, such as hot flashes, night hormones checked” because they perceive changes sweats, cold flashes, and palpitations, are experienced in their ovarian function. But since fluctuating hor- at least to some degree by almost 90 percent of mones are the very hallmark of the perimenopausal women during their transition to menopause. The transition, determining their levels on any given day average duration of hot flashes for a woman undergo- is of little diagnostic or therapeutic import. It is use- ing natural menopause is approximately two years, Determining
levels of estrogen
is of little help.
taking a generally adequate replacement dose.
result from a sudden change in heat regulation. Hot Follicle-stimulating hormone (FSH) levels do not flashes vary in intensity, can last a few seconds to generally influence the management of a menopausal several minutes, and recur as frequently as every 10- or perimenopausal woman. For example, if the patient is 52 years of age, has stopped menstruating, The exact cause of hot flashes is not completely and is experiencing hot flashes, one would treat her understood. Although they coincide with luteinizing regardless of her FSH level. If she is 48 and has hot hormone (LH) surges, the fact that hot flashes occur flashes and irregular periods, her FSH level may be after hypophysectomy indicates that they are not entirely normal, mildly elevated, or within the directly caused by LH. They do correlate with menopausal range on any given day. Whatever her decreasing estrogen levels but not necessarily with FSH level, a regimen of oral contraceptives (OCs) or low estrogen levels. Women with gonadal dysgenesis possibly sequential HRT is warranted.
only experience hot flashes after estrogen is first There are only two scenarios during peri- administered and then withdrawn. Estrogen replace- menopause in which an FSH level is useful: the ment will stop hot flashes but may require higher than woman with premature menopause who requires physiologic premenopausal levels. All vasomotor definitive diagnosis and the perimenopausal woman symptoms will eventually subside with or without who has been managed on OCs for several years and requires evaluation to determine if it is time to switchher to HRT. In the latter case, I measure FSH at the What menstrual changes can be expected in
end of her placebo interval. Alternatively, she can be the perimenopausal period?
switched to HRT without first ordering an FSH when As the ovaries age and most of the primordial fol- she starts having menopausal symptoms during her licles are used up, less potent and less responsive folli- cles are recruited. This leads to shorter menstrual ᮣ C L I N I C A L U P D A T E
High-dose nonsteroidal anti-inflammatory drugs,started with a double (loading) dose at the first sign Progestin Regimens for
of menses and continued for the duration of the Cycle Regulation
entire menstrual period, will generally reduce drasti-cally the amount and often the duration of bleeding.
Micronized progesterone
In fact, nonresponse to this regimen is an indicationfor further workup, which may include hysteroscopy Medroxyprogesterone
or a saline-infusion sonogram to look for polyps or Norethindrone acetate
Whichever regimen is chosen, progestin should be used either from the first to the 10th day of eachmonth or for 10 consecutive days whenever the patient cycles with deficient progesterone levels and rapidly has failed to menstruate spontaneously for five or six declining estrogen levels in the second half of the weeks. The latter regimen is indicated for the patient cycle. The result is a shortened bleeding interval; pre- who skips the occasional period and then suffers from menstrual spotting; and premenstrual signs of rap- severe menorrhagia with the next menses. Progestin idly declining estrogen levels, such as hot flashes, regimens for cycle regulation include micronized pro- night sweats, irritability, depression, and estrogen- gesterone 400 mg once daily for 10 days, medroxy- withdrawal headaches—“perimenopausal premen- progesterone acetate (MPA) 10 mg once daily for 10 strual syndrome (PMS).” In some cycles, ovulation is days, and norethindrone acetate 5 mg daily for 10 days skipped altogether, resulting in a long proliferative (Table 1). The advantages of natural progesterone phase followed by menorrhagia, which can be severe.
over MPA or norethindrone acetate are fewer PMS- While the menstrual pattern of both bleeding like side effects and lack of adverse effect on the lipid interval and amount may vary considerably among profile. The main disadvantage is the cost.
women, the pattern for an individual woman remains Oral contraceptives have been approved by the remarkably constant for decades. Therefore, these Food and Drug Administration for use in peri- perimenopausal changes—alternating long and short menopausal women. Products containing 20 µg of cycles and profuse, scant, or no bleeding—at times estradiol should be used in this age group. If break- are of considerable concern to most women. A brief through bleeding does not resolve, the estradiol dose explanation of the physiology leading to these can be increased to 0.35 µg, but a 50-µg pill poses too changes as well as reassurance that they are normal great a risk in this older population. Patients should and to be expected is often all the intervention that is be followed with blood pressure checks and lipid needed. Of course, if bleeding is excessive or the evaluation within two to three months after initiation patient requests regulation of her cycle or treatment of PMS, any of several modalities can be offered.
Who should undergo an endometrial biopsy?
When and how should perimenopausal
An endometrial biopsy is indicated in any patient menstrual changes be treated?
over 40 who has long-standing bleeding abnormalities The option to treat perimenopausal menstrual or who is at increased risk for endometrial hyperpla- changes should be offered to every patient, but the sia or cancer because of obesity and/or anovulatory decision to treat should be left up to the individual bleeding. An endometrium of >5 mm on pelvic ultra- woman. Cycle regulation can be achieved either with sound in a postmenopausal woman is also an indica- monthly administration of a progestin, thereby imi- tion for endometrial biopsy. When in doubt—biopsy.
tating the natural luteal phase, or by overriding ovar-ian function altogether by imposing an exogenous How should perimenopausal PMS be treated?
It is very common for women in their 40s to experi- With intermittent anovulatory and irregular ence an increase in premenstrual symptoms. Treatment cycles, excessively heavy bleeding is often a problem.
depends on the predominant symptomatology. ᮣ C L I N I C A L U P D A T E
avoids abrupt estrogenreduction, which can trigger Dietary Guidelines for Healthy American Adults
the very symptoms that arebeing treated. If the pa-tient’s managed-care plan The American Heart Association Eating Plan for Healthy Americans is based on these
AHA dietary guidelines:
• Total fat intake should be no more than 30 percent of total calories.* ing the placebo week,either a 0.05-mg estradiol • Saturated fatty acid intake should be eight to 10 percent of total calories.
• Polyunsaturated fatty intake should be up to 10 percent of total calories.
• Monounsaturated fatty acids should make up to 15 percent of total calories.
• Cholesterol intake should be <300 mg per day.
• Sodium intake should be <2400 mg per day, which is about 1⁄ teaspoons of sodium chloride.
• Carbohydrate intake should make up 55-60 percent or more of calories, with emphasis on increasing sources of complex carbohydrates.
• Total calories should be adjusted to achieve and maintain a healthy body weight.
inhibitor (SSRI) is almostalways successful. For some *Some people misinterpret this to mean that each food or each recipe should have <30 percent of its calories come from fat. The guideline applies to total calories eaten over several days, such as a week. If it is applied to single foods, the “30 percent of calories from fat” guideline will cause many foods that fit into a well-balanced eating plan to be (From www.americanheart.org/Heart_and_Stroke_A_Z_Guide/dietg.html) month on a low dose that isincreased for the last weekor two of the cycle. I find Irritability, headaches (including migraines), insomnia, Prozac (fluoxetine) ideal for this indication because of hot flashes, and night sweats limited to the last seven to its long half-life and excellent safety profile. However, 10 days of an otherwise regular, possibly somewhat sometimes only the combination of an OC along with shortened, menstrual cycle may indicate rapidly an SSRI gives adequate symptom relief.
decreasing estrogen levels. Treatment consists of either Rapidly growing fibroids and tender breasts are a estrogen supplementation during the symptomatic symptom of estrogen excess, which is a common time period only or of overriding the cycle altogether occurrence in the perimenstrual phase. Increasingly by imposing an external cycle with OCs. The latter is high FSH levels are required to stimulate the remain- the preferred option in nonsmokers who are begin- ing ovarian follicles and may result in intermittent ning to experience intermittent cycle irregularities.
estrogen excess. The most effective way to avoid this For premenstrual estrogen supplementation, a is by overriding ovarian function with OCs. Masto- transdermal estradiol patch of 0.25-0.5 mg is quite dynia often responds to 800 IU daily of vitamin E.
convenient. Alternatively, a daily 0.3-mg conjugatedestrogen pill starting on the first day of symptoms When is it time to start HRT?
and continued until the onset of the next cycle also Once ovarian function has ceased entirely, HRT is indicated. The traditional HRT regimen in the United In perimenopausal women, any of the OCs con- States has for many years been Premarin (conjugated taining 20 µg of estrogen work well. The estrogen estrogens) 0.625 mg from day one through 25 of every dose may be increased to 35 µg when there is persis- calendar month plus Provera (medroxyprogesterone tent breakthrough bleeding on the lower dose. A acetate) 10 mg from day 16 through 25, followed by a product with a small dose of estrogen during the pill-free interval and a withdrawal bleed until the end placebo week is ideal in this age group because it of the month. This regimen has two major drawbacks: 170 CORTLANDT FORUM
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Ortho-Prefest. However, these continuous combined American Heart Association Scientific
regimens rarely work for perimenopausal and early menopausal women with an endometrium still Position on Exercise
responsive to estrogen stimulation and intermittentendogenous ovarian function. They are best reserved Physical inactivity has been established as a major risk for women already several years into the menopause.
factor for the development of coronary artery disease. It also Other than better patient acceptance, there is no contributes to other risk factors, including obesity, high blood known benefit to the continuous combined regimen pressure, and a low level of high-density lipoprotein cholesterol.
Even moderate-intensity physical activity, such as brisk walking, is beneficial when done regularly for a total of 30 minutes or Transdermal therapy is preferable in patients with high triglyceride levels because, unlike oral estrogen, Activities that are especially beneficial when performed
transdermal administration does not increase triglyc- regularly include:
eride levels. In the patient with an absorption prob-lem, administration is also advantageous. Some patients simply prefer not to take pills. Progesterone is avail- able in a combined estrogen/progestin patch that is soccer and basketball,that include continuous marketed mostly as a continuous combined regimen.
However, in perimenopausal women, the patch is bet- ter used in a sequential fashion, by alternating an (From www.americanheart.org/Heart_and_Stroke_A_Z_Guide/exercise.html) estrogen-only patch for two weeks with two weeks ofthe 250/50 estrogen/progestin patch.
First, many women will get estrogen-withdrawal How should hot flashes be treated in some-
symptoms, such as hot flashes and headaches, during one who cannot take estrogen?
the pill-free days. Second, the high MPA dose of 10 There are several alternate treatments available mg is poorly tolerated by most women, giving them for hot flashes. Unfortunately, none is as effective as PMS-like symptoms, such as fluid retention and mood estrogen, and many have a high rate of side effects swings. A more updated sequential HRT regimen when administered in doses large enough to affect hot consists of continuous estrogen every day of the year flashes. Bellergal (phenobarbital, ergotamine, and with a progestin added from days one through 12 or alkaloids of belladonna), which has been used for 14. The most commonly used progestin is still years in the treatment of hot flashes, is no more effec- Provera, but the lower dose of 5 mg given for a few tive than placebo when evaluated in controlled fash- more days has been shown to provide equal endome- ion. Progestins are effective, but as exogenous steroids, trial protection with fewer side effects than 10 mg.
they raise the same concerns as estrogen. The best-tol- Some women do not tolerate MPA in any dose. For erated and most effective nonestrogen treatment for these, a trial of micronized progesterone 200-300 mg a hot flashes is transdermal clonidine 100 µg applied day for days one through 12 at bedtime may work.
once a week. Alternate regimens include veralipride Another option is to take an even lower MPA dose 100 mg daily and methyldopa 250-500 mg daily.
of 2.5 mg daily along with estrogen. This, after some There is also increasing evidence that phytoestro- irregular breakthrough bleeding for the first few gens can be taken safely by women who have estro- months, will result over time in an atrophic en- gen-dependent neoplasms for at least partial relief dometrium with no bleeding at all. Two new products from vasomotor symptoms. The dose found effective Ortho-Prefest (estradiol/norgestimate) and Femhrt in a controlled setting is 60 g of soy protein a day. Less (ethinyl estradiol/norethindrone) have recently information is available for black cohosh, which is said become available for continuous combined HRT.
to bring relief in the dose of 20 mg b.i.d. Vitamin E at Both are preferable over some of the MPA-containing 800 IU daily is also taken for the relief of hot flashes; agents because of a better lipid profile, especially for at the very minimum, it is a good antioxidant. ᮣ C L I N I C A L U P D A T E
What nonhormonal treatments are valuable in
immobility lead to marked bone loss, the type and the management of menopause?
amount of exercise required to either prevent loss or The best-reasoned HRT regimen cannot com- actually build new bone are unclear. Most likely, more pensate for a poor diet and an unhealthy lifestyle. In vigorous exercise than most people are willing and women of this age group, a major complaint is weight able to sustain over prolonged periods of time would gain, most of which can be blamed on lack of exercise be necessary. Regular exercise certainly has an impor- and less-than-ideal dietary habits (Table 2). There tant place in the maintenance of an attractive and seems to be, however, a genuine tendency to put on healthy body, including healthy bones.
about 10 pounds around age 50, regardless ofmenopausal status and, if a woman is menopausal, Are complementary approaches safe?
regardless of whether she is on HRT or not. While Nowadays, many patients are using complemen- highly undesirable in our culture, putting on a few tary medicines. Are these safe and effective for extra pounds pads the wrinkles and reduces the risk of menopausal women? The role of complementary osteoporosis. Unfortunately, it also increases the risk medicine in the management of the perimenopause of heart disease. Careful attention to diet and exercise at this point is controversial, mostly due to lack of (Table 3) can keep this weight gain to a minimum. If solid evidence as to its efficacy. Nevertheless, vast weight loss is desired, a moderate-protein, low-fat, numbers of our patients are taking this approach, low-carbohydrate diet combined with regular exercise either alone or in combination with conventional is generally the most successful. A fasting lipid profile prescriptions, often without disclosing such use to A diet rich in soy
proteins may be
beneficial.
source, but most women will need to add a supple- benefits, though the epidemiologic evidence is cer- ment to reach the recommended calcium dose.
tainly compelling. Controlled studies assessing the Calcium supplements should be ingested with food in effects of herbal remedies on postmenopausal three to four portions to achieve the best absorption.
health are under way. Until their results become Calcium citrate maleate appears to be slightly better available and until herbal products are subjected to absorbed than calcium carbonate but is generally the same quality-control standards as other medica- much more expensive. Calcium is an important anti- tions, we have to tell our patients that they are, resorptive agent that is of limited benefit when taken essentially, practicing experimental medicine on alone, but it significantly enhances the action of other themselves when they use yet-to-be-tested products.
antiresorptive agents used in the prevention and And most important, we have to remind our management of osteoporosis, including estrogen.
patients that “natural” does not equal “safe.” Some The benefits of a regular exercise program on both of the most potent poisons on this planet are natur- cardiovascular as well as bone health are numerous.
al herbs. On the other hand, encouraging women to Strong muscles alone enhance well-being and longevi- consume a diet rich in soy proteins, which contain ty, as well as prevent falls and thereby fractures. While many plant estrogens, is more than likely beneficial it is well-established that complete weightlessness and Part 2, on management of late menopause, will appear next month.
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Source: http://www.regulabuerki.ch/files/pdf/en/Menopause%20Management,%20Part%201%20(Cortlandt%20Forum,%20July%202000).pdf