Associated Content | Figure 1 | Figure 2 | Figure 3 | Figure 4

Urogenital symptoms

Schiff: One of the major short-term benefits of HRT is relief of urogenital symptoms. Dr. Sarrel, can you tell us what’s new in this area?

Sarrel: Like the vagina, the urethra and the bladder are lined by cells that have estrogen receptors and that react to estrogen depletion. A deficiency in estrogen leads not only to atrophy in the vaginal wall but also to atrophy within the urethra and the bladder. Studies of estrogen’s effect on blood flow to the urethra indicate that about 25% of intraurethral pressure is determined by urethral blood flow.¹⁷ So with a decrease in estrogen or an estrogen depletion state, there’s a decrease in intraurethral pressure.

As a result, we see urge incontinence and urinary frequency starting to show up in women in the perimenopause and menopause. Of course these problems become much more prevalent later on in older women. In the WEST [Women’s Estrogen for Stroke Trial] study, we had about 200 patients over age 80 who had significant urgency problems.¹⁸ They had small, shrunken bladders and were waking frequently at night to urinate. My impression is that estrogen helped those older women get through the night better and reduced their problems of urgency and frequency.

Schiff: And what about the more common urogenital complaint—the problem of vaginal dryness and pain associated with intercourse?

Sarrel: The best estimates are that about 40% of women experience vaginal dryness to a degree that affects their sexuality—an association that has been reported in the medical literature for decades.¹⁹ What is the real cause of vaginal dryness? I think the most important cause is reduced vaginal blood flow associated with loss of ovarian estrogen. In the early 1980s, Semmens and Wagner showed that giving estrogen increased vaginal blood flow and effectively treated vaginal dryness.²⁰

In our own studies, we have looked at the response of vaginal dryness to both oral and vaginal estradiol.²¹ The bottom line is that a very small dose of estradiol, within 4 weeks’ time, can reverse the problem of vaginal dryness and eliminate a source of dyspareunia. That’s significant, since dyspareunia can mean the end of sexual relations. Women are unable to respond as they had been accustomed to respond, and their sexual partners become acutely aware of that. We reported that in 60% of cases, male partners had developed reactive erectile problems.²² So when you treat the woman, you’re treating the man as well.

Schiff: It’s clear that vaginal dryness is a disturbing and common symptom in menopausal women and that estrogens are an effective treatment. My question again is why do 80% of women stop HRT within 2 years of starting it if this treatment is providing such effective relief?

Sarrel: One answer is that if the couple can reconnect and reestablish a healthy sex life, the sex response itself helps maintain vaginal secretion and vaginal pH. That was one of the early Masters and Johnson findings. So estrogen therapy may provide the basis for reestablishing regular intercourse and then be abandoned when intercourse itself proves therapeutic.

Loss of the partner may also be significant. Women in their 60s are certainly less likely to have a partner than women in their late 40s or early 50s because of the higher mortality of men in this age group. By age 75, three out of four women have no sexual partner. So lack of a partner removes one of the motivating factors to continue hormone replacement.

Another reason younger postmenopausal women—the 49- to 53-year-old age group—reject or discontinue hormone replacement is fear of breast cancer. As we reported at a NAMS meeting several years ago, that’s the primary reason these younger women don’t take advantage of HRT.²³ In older women or women more than 2 years past their last menstrual period, adverse effects of therapy are the main reason for discontinuance. It’s something of a paradox that younger postmenopausal women may be the most highly motivated to use HRT, for vasomotor symptoms as well as sexual problems, but they’re also the most fearful of using it because of their fear of cancer. That underscores the need for clinicians to understand women’s anxieties and know how to respond to them.

Nachtigall: Still another reason why women don’t continue using estrogen when it corrects their vaginal dryness may be estrogen’s very effectiveness in fixing that problem. The vaginal epithelium is one of the few tissues you can almost totally regenerate, even 20 years after the menopause. When it’s restored, that effect lasts for a long time, anywhere from a year to 5 years. So a woman can discontinue estrogen and still feel fine for some time. In fact, she may not associate the effect with the treatment, or she may forget how she felt before the treatment.

Sarrel: Another point to consider is the impact of the progestin component. In our study, we found that when MPA was added to estrogen, vaginal dryness and pain with intercourse returned in more than 20% of the women.²¹ That was certainly a reason for early discontinuance in those women. So one of our considerations in prescribing combined therapy is achieving a proper balance of estrogen and progestin so that the overall effect is therapeutic rather than attenuating.