Approach to the Perimenopausal Patient

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Applied Evidence

Approach to the Perimenopausal Patient

J Fam Pract. 2002 March;51(3):271-276

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References

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Irritability and mood swings are common climacteric complaints. Women often compare them with their earlier premenstrual symptoms. Studies of depressive symptoms in menopausal women indicate that menopause is not associated with increased rates of major depression.¹⁹ Stressful life context and poor health status appear to be more important risk factors for depression than symptoms of menopause in climacteric women.²⁰

Many perimenopausal women complain of poor sleep, often attributed to nocturnal hot flashes. Subjective impairment of sleep quality that is associated with climacteric vasomotor symptoms does not manifest as abnormalities in polysomnographic sleep recordings.²¹ It does not appear to be related to sleep apnea.

Sexual dysfunction is common in women at midlife and beyond. Dyspareunia, associated with vaginal dryness, increases in frequency with increasing time after menopause.⁹ The other complaint is decreased libido. Multiple factors may contribute to lack of sexual interest. Both aging and the menopause are independently associated with decreases in sexual responsiveness.²² The roles of declining endogenous sex steroid hormones in this process have not been elucidated.

Treatment

Vasomotor symptoms

Table 1 summarizes treatment options for vasomotor symptoms. Numerous well-designed clinical trials have demonstrated the effectiveness of oral or transdermal estrogen replacement therapy (ERT) for hot flashes.^18,23-25 Low-dose oral contraceptive formulations are approved until 50 years of age for nonsmoking women.²⁶ In a well-designed randomized controlled trial (RCT) of 93 women, low-dose estrogen (0.625 mg conjugated equine estrogens daily) plus 1.25 mg methyltestosterone daily was shown to be more effective than low-dose estrogen only and as effective as high-dose estrogen (1.25 mg conjugated estrogens daily).²⁷

Phytoestrogens may be helpful, but have not yet been studied extensively. One RCT²⁸ of 104 postmenopausal women comparing ingestion of 60 g soy protein daily with that of 60 g casein (placebo) daily showed a 45% relative reduction of hot flashes at 12 weeks in the group taking soy versus the control group. A second RCT²⁹ of 51 women comparing soy protein with carbohydrate placebo showed a decrease in severity, but not frequency, of hot flashes. Another well-designed RCT³⁰ including 69 women treated with 40 g soy daily versus whey protein for 24 weeks showed no difference between treatment groups and improvement in symptom scores over time in both groups. It is difficult to include a 40-g to 60-g protein supplement in the daily diet because of the accompanying caloric intake required. Recent reports of randomized placebo-controlled trials of black cohosh³¹ and dong quai³² and a systematic review³³ of controlled trials of red clover have found no benefit.

Alternatives to estrogen for treatment of hot flashes include methyldopa, clonidine, transdermal progesterone, and megestrol acetate. Megestrol, which reduces symptoms by 70%, appears to be the most effective of these.³⁴ Although long-term use of megestrol acetate by cancer survivors for the treatment of hot flashes has been demonstrated to be effective and well tolerated,³⁵ it is not customarily used at menopause. A 20% reduction in hot flashes can be expected with clonidine at a dose of 0.1 to 0.2 mg daily,^34,36 although this regimen may cause an increase in difficulty sleeping³⁷ as well as dry mouth, constipation, and low blood pressure. Transdermal progesterone cream alone has been shown to improve vasomotor symptoms, although without protective effect regarding bone loss.³⁸ One small study³⁹ of behavioral approaches showed symptom reduction with deep-breathing relaxation techniques. Pilot studies of sertraline,⁴⁰ venlafaxine,⁴¹ and paroxetine⁴² show promise in the treatment of hot flashes.

The remainder of this article focuses on hormonal treatment effects and risks for menopausal women. A summary appears in Table 2.

TABLE 1
TREATMENT OF VASOMOTOR SYMPTOMS

Strength of Recommendation	Treatment	Comment
A	Estrogens	Many preparations with both oral and transdermal delivery have been studied
A	Estrogen + MPA	Other progestins not well studied
B	Transdermal progesterone	One RCT³⁸
B	Estrogen + testosterone	One RCT²⁷; long-term safety is a theoretical concern
B	Megasterol	Cohort³⁵; long experience with cancer patients gives some assurance of safety
C	Behavioral approaches	One small RCT³⁹; deep breathing was beneficial
C	Clonidine	Small RCTs^36,37 with important loss of subjects because of side effects
D	Antidepressants	Pilot studies of sertraline,⁴⁰ venlafaxine,⁴¹ and paroxetine⁴²
D	Phytoestrogens	Conflicting RCT results
D	Exercise	Weak observational studies suggest benefit^74,76
No benefit seen
B	Black cohosh	No benefit seen in one RCT³¹
B	Dong quai	No benefit seen in one RCT³²
B	Red clover	No benefit seen in systematic review³³
Grades of recommendation are based on Oxford Centre for Evidence-Based Medicine guidelines.
MPA denotes medroxyprogesterone; RCT, randomized clinical trial.

TABLE 2
SUMMARY OF RISKS AND BENEFITS OF TREATMENTS FOR PERIMENOPAUSAL SYMPTOMS

Treatment	VMS	Mood	Libido	Bone	CAD	Breast CA
Estrogens	Benefit	Benefit	No benefit	Benefit	Uncertain	Risk
Estrogen + MPA	Benefit	? benefit	No benefit	Benefit	Uncertain*	Risk†
Progesterone	Benefit	Risk	No benefit	NS	Uncertain	NS
Testosterone	Benefit	NS	? benefit	Benefit	NS	NS
Phytoestrogens	? benefit	NS	NS	No benefit	NS	NS
DHEA	NS	? benefit	? benefit	NS	NS	NS
* Not beneficial for secondary prevention. † Increased risk over estrogen alone.
CA denotes cancer; CAD, coronary artery disease; DHEA, dihydroepiandrosterone; MPA, medroxyprogesterone acetate; NS, not studied; VMS, vasomotor symptoms.

Mood disorders