Genital complaints

After the menopause, the urogenital mucosa becomes thinner, less elastic, and less vascular. By late menopause the vagina is shortened and narrowed, with a thin, friable surface. Vulvovaginal symptoms, which do not necessarily parallel clinical findings, include dryness, pruritis, discharge, dyspareunia, and postcoital bleeding. Nevertheless, many older women report a satisfactory sex life without hormone replacement therapy. In the Massachusetts Women’s Health Study, factors such as marital status and sexual dysfunction of partner, physical and mental health, and cigarette smoking had a greater impact on sexual functioning than menopause status.

Oral, transdermal, and intravaginal oestrogen (cream, tablet, or vaginal ring) have been shown to relieve vaginal symptoms in at least ten randomized placebo-controlled trials. Among HERS women treated with oral oestrogen, 61% on hormone replacement therapy and 47% on placebo reported improvement in genital dryness.

Topical oestrogen appears to be more effective for vaginal dryness than oral oestrogen and may be required in addition to systemic oestrogen in some women. A vaginal ring containing 2 mg of oestradiol can be inserted by the patient or health-care provider once every 3 months. Oestradiol tablets (oestradiol hemihydrate  – Vagifem) are inserted vaginally daily for 2 weeks and twice a week thereafter. Oestradiol or Premarin creams can be applied by plastic applicator or finger one to three times a week. The vaginal ring and tablets do not increase circulating oestrogen levels, and are considered safe for breast cancer survivors, although some oestrogen is systemically absorbed. For women who wish to avoid oestrogen, vaginal dryness can be managed with vaginal moisturizers and lubricants. Replens decreases vaginal pH, as does oestrogen.

Table Topical oestrogen preparations for atrophic vaginitis*
Preparation Administration Comment
Conjugated oestrogen (0.625 mg)
Premarin Vaginal Cream
0.5-2 g/day intravaginally Reduce to one-half initial dosage over 1-2 weeks to maintain vaginal mucosa at the lowest possible dose
Oestriol (0.01%)
Ortho-Gynest Vaginal Cream
Initial: 1-2 applicatorsful/day for 1-2 weeks Reduce to one-half initial dosage over 1-2 weeks to maintain vaginal mucosa at the lowest possible dose
Maintenance: 1 applicatorful 1-3 times/week
Oestriol (0.1%)
Ovestin Vaginal Cream
Initial: 2-4 g daily for 1-2 weeks Reduce to one-half initial dosage over 1-2 weeks to maintain vaginal mucosa at the lowest possible dose
Maintenance: 1 g 1-3 times/week
Oestradiol (25 Вµg)
Vagifem
Initial: 1 tablet inserted vaginally once daily at same time each day
Maintenance: 1 tablet inserted vaginally twice weekly
Oestradiol ring (75 Вµg)
Estring
Insert ring into upper one-third of vaginal vault Keep in place continuously for 3 months, then remove and replace with new ring
*Attempt to discontinue or taper medication at 3- to 6-month intervals.
The only topical oestrogen therapy for which there is no evidence of endometrial stimulation.

Libido

Although adequate lubrication can improve arousal and orgasm, there is no evidence that reduced sexual desire with onset during the menopause transition is caused by oestrogen deficiency or improved by oestrogen replacement. In fact, oral oestrogen increases sex hormone binding globulin, which can then reduce bioavailable testosterone. In two clinical trials, oestrogen plus testosterone improved sexual enjoyment, desire, and arousal more than oestrogen alone. Testosterone regimens shown to improve libido produce circulating testosterone levels above the physiological range, with potential side effects of acne, facial hair, and deepening of the voice. Trials of low-dose testosterone patches are under way. Tibolone, an oestrogen substitute with androgenic effects, has been shown in clinical trials to improve vaginal dryness, libido, and sexual satisfaction.

Urinary complaints

Urinary tract symptoms attributed to oestrogen deficiency include dysuria, frequency, nocturia, stress incontinence, urge incontinence, coital incontinence, and urinary tract infection. Of these only the frequency of recurrent urinary tract infection has been shown in clinical trials to be reduced by oestrogen treatment, presumably by reversing the postmenopausal decrease in vaginal flora and increase in vaginal pH caused by lack of oestrogen. However, hormone replacement therapy did not prevent urinary tract infections in women without a prior history of urinary tract infections.

There is no good evidence that hormone replacement therapy protects against stress or urge incontinence. In the largest reported trial, women assigned to oestrogen plus a progestogen reported increased incontinence compared to women assigned to placebo.

Hormone replacement therapy to prevent chronic diseases

The last 25 years was a time of great enthusiasm for the concept of oestrogen deficiency diseases, and the potential of hormone replacement therapy to prevent diverse conditions that are common in later life. Observational studies reported that women using hormone replacement therapy had fewer fractures, less heart disease, less colon cancer, and less dementia, but other factors could explain some or all of these putative benefits. For example, women physicians in Britain with continued hormone use are more likely than non-hormone-using physicians to report a healthy diet and vigorous physical activity. Only randomized, placebo-controlled clinical trials that control for the effects of known and unknown differences between women who chose to take or continue hormones can provide the basis of “evidence-based medicine”. Nowhere has the importance of clinical trials been so evident as in recent hormone replacement therapy trials where results differed from expectations, as discussed below.

 

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