Irregular menses

A common symptom for perimenopausal patients is irregular menses.[1] Women can be advised that they are expected to have shorter cycles and longer cycles with heavier or lighter bleeding. There are other potential anatomic causes of menorrhagia that are common in women during their perimenopausal years, such as uterine fibroids, endometrial polyp, and endometrial hyperplasia. If bleeding is prolonged, excessive, or occurs between menses, evaluation is indicated. A transvaginal ultrasound and possible endometrial biopsy should be considered. In addition, endocrine evaluation should be considered with thyroid-stimulating hormone (TSH), as hypothyroidism can cause oligomenorrhea and menorrhagia.

If the bleeding is bothersome, it can be controlled with hormonal contraceptives, cyclic progestin, or continuous progestin. Women with heavy menses may benefit from the use of oral contraceptives, which will lighten and regulate menses. In addition, oral contraceptives manage vasomotor symptoms. With extended cycles, women can use cyclic oral progestin to make menses more predictable. Continuous progestin, by tablet, injection, implant, or intrauterine device, can be provided to minimize bleeding during the menopause transition. The progestin IUD, which lasts for five years, can be used to manage perimenopausal menorrhagia and then be removed following one year without menses.[10]

Vasomotor symptoms

Hot flushes and night sweats occur in 80% of women during late perimenopause and menopause.[2] The sudden increase in core body temperature extends from chest to neck and face, results in sweating, and may cause significant tachycardia. When the body temperature drops, women commonly become chilled. In addition to the disruption by the heat, sweating, and shivering, women may feel anxiety during and following the hot flush.

The severity and duration of these common symptoms are variable. The frequency and duration of vasomotor symptoms are variable.[11] Although most women have vasomotor symptoms, most have a significant decrease in frequency and intensity within four to five years. Interestingly, women may have vasomotor symptoms into their seventies, with 9% reporting ongoing hot flushes.

Typically vasomotor symptoms are more frequent during sleep and may disturb sleep. Sleep disruption can have a serious adverse effect on perimenopausal and menopausal women. Almost half of women have difficulty sleeping in their late perimenopause and early postmenopausal years.[12] The sleep disturbance can lead to decreased cognitive function, mood changes, and decreased overall quality of life.

Although severe hot flushes and night sweats may adversely affect the quality of life, many postmenopausal women do not require medical treatment. Since these symptoms decrease over time, women may consider no therapy for mild and moderate hot flushes. Unfortunately, methods of stress reduction, such as exercise, have not been shown to lessen vasomotor symptoms.[13] Studies examining alternative therapy, such as black cohosh, show very minimal effect when compared to a placebo. Phytoestrogens, such as isoflavones found in soy products and lignans found in flaxseed, are weak estrogens with limited effect on hot flushes. Systematic reviews have shown no significant improvement with plant estrogens.[14] Although the effectiveness of stress management, over-the-counter herbal medications, and phystoestrogens has been shown to have minimal effect on hot flushes, women commonly try these treatments.[15] It is important for health-care providers to inform patients of the ineffectiveness of these treatments and offer medical options for treatment of moderate and severe vasomotor symptoms.

The standard treatment for vasomotor symptoms continues to be hormone therapy. Estrogen (± progestin) is highly effective at lessening these symptoms. Three-fourths of women have marked reduction or elimination of hot flushes and night sweats on hormone therapy, and the remainder have some reduction.[11] No treatment has been shown to be more effective than hormone therapy for vasomotor symptoms. All forms of hormone therapy, including low doses of oral and transdermal estradiol, are effective. The current FDA recommendation is to use the lowest dose for the shortest time required to manage symptoms.

Other treatments, including selective serotonin reuptake inhibitors (SSRIs), gabapentin, clonidine, and progestins, have been used with moderate success for control of vasomotor symptoms (Figure 31-3). One SSRI, paroxetine at 7.5 mg qhs, is now FDA approved for the treatment of hot flushes with minimally increased effectiveness as compared to the placebo.[16] Other SSRIs and serotonin-norepinephrine reuptake inhibitors (SNRIs) have also been shown to have a modest effect compared to placebo, including fluoxetine, sertaline, venlafaxine, escitalopram, and desvenlafaxine. Although the effectiveness, as compared to a placebo, is modest, these are medications to consider for women who are not candidates for hormone therapy. Some caution should be made when prescribing SSRIs or SRNIs for women with breast cancer who are using tamoxifen, as these medications may lower the availability of the active metabolite of tamoxifen. This is described in a black box warning for the use of paroxetine for vasomotor symptoms.

Gabapentin has been shown to be moderately effective in reducing vasomotor symptoms. Although not FDA approved for this use, studies suggest that a significant reduction in night sweats occurs when taken at bedtime.[17] Typical doses are 900 mg, although the medication is often started at 300 mg and slowly increased. The side effects, including dizziness and fatigue, can be problematic. When compared to conjugated equine estrogen, gabapentin was equivalent, but at a high doses. As with SSRIs and SSNIs, this is a reasonable alternative therapy.

Clonidine effectively prevents tachycardia associated with temperature elevation and in some studies decreases hot flushes, although studies have been inconsistent.[18] However, because of side effects such as dizziness and dry mouth, this medication may not be tolerated. The patch form can be considered for extended effect.

Progestins alone are less effective than estrogens at decreasing hot flushes, but can reduce hot flushes in high doses. Both norethindrone acetate and depo-medroxyprogesterone acetate in high doses significantly decrease hot flushes.[19] Megestrol acetate, which has been used to treat breast cancer, has also shown to reduce hot flushes.[20] This medication stimulates appetite and can be associated with weight gain.

In summary, vasomotor symptoms are common with 80% of women reporting these symptoms. Most women can tolerate hot flushes, although they are debilitating for about 10% of women.[11] For women with significant sleep disturbance or hot flushes that impact their quality of life, estrogen or estrogen + progestin are the most effective therapy. Overtime, the dose can be reduced and eventually discontinued. When hormone therapy is not an option, SSRIs and gabapentin can be considered.

Vaginal/vulvar atrophy

The external genitalia and vaginal tissue will atrophy in the absence of estradiol from the ovary. There is a thinning of the vulva and a decrease in the elasticity. The urethra may change position with a decrease in vaginal muscular, and the anterior vaginal wall may prolapse, leading to a cystocele. The posterior vaginal wall may also have decreased muscular tone that leads to a rectocele. The thinned vaginal tissue loses its rugae, and there is a decrease in natural lubrication. There is an increased risk of uterine prolapse or development of an enterocele. Unlike vasomotor symptoms, these changes worsen over time.

Common symptoms include dryness and dysparuenia. Many women note severe dryness, although only 25% seek therapy.[21] Women may have discomfort when physically active. Severe atrophy can cause bleeding when sexually active. There is an increased risk for bladder infections and stress incontinence. Rectal incontinence is also increased in menopausal women.

Some women have effective treatment with lubricants alone. This is a reasonable therapy for women with dryness alone, but it will not be effective for women with atrophy.

The most effective treatment of marked atrophy is systemic or vaginal estradiol in low dose. For women with vasomotor symptoms, the systemic hormone therapy is typically effective for vaginal atrophy. For women without hot flushes, vaginal estrogen alone is indicated. This medication comes in the form of a tablet, cream, and ring; all methods have been shown to improve atrophy.[22, 23] There is a minimal effect on serum estradiol levels with topical vaginal and vulvar treatment and no effect on endometrial development.[24] However, there is little data of the effect on estrogen-sensitive cancers. It is important to inform patients that very low doses are required for effective improvement in atrophy.

Vaginal estrogen is highly effective for atrophy, but it has not been shown to improve stress incontinence. It will not correct vaginal or uterine prolapse. For these conditions, surgical intervention may be indicated.

Sexual function

The effect of atrophy on dysparuenia has a direct effect on sexual function. Women with atrophy are likely to avoid sexual activity. With very severe atrophy, the vulvar tissue is friable and can be injured. In addition, there can be constriction of the vaginal vault, which prevents intercourse.[25] The treatment of vaginal atrophy can markedly decrease pain with intercourse and improve sexual function. In addition to vaginal estrogen, physical therapy may be required for women to resume sexual activity.

Sexual function may be impacted by an adverse effect of severe vasomotor symptoms on the quality of life, especially if normal sleep is adversely impacted. However, the direct effect of steroid hormones on sexual function, aside from the influence on vaginal atrophy and night sweats, is unclear.

Limited research has shown an improvement in sexual function of women on estrogen use.[26] Testosterone, given with estradiol in women with oophorectomy, has been shown to increase sexual interest and sexual activity.[27] The Cochrane Database identified that there is limited data to support the use of testosterone, but the long-term risk is not clear.[28] Currently, in the United States there is no form of testosterone that is FDA approved for sexual dysfunction, although methyltestosterone plus esterified estrogen are available for the treatment of vasomotor symptoms.

Before considering hormonal therapy, it is critical to consider relationship issues. Even women in stable relationships can benefit for therapy. Studies support the effectiveness of behavioral therapy for sexual dysfunction.[29] The most effective therapy for many women may be counseling by a skilled therapist.