Advertisement

Genitourinary symptoms in the menopausal transition

  • Bradley J. Van Voorhis
    Correspondence
    Requests for reprints should be addressed to Bradley J. Van Voorhis, MD, Department of Obstetrics and Gynecology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, Iowa 52242
    Affiliations
    Department of Obstetrics and Gynecology, University of Iowa Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA
    Search for articles by this author
      Irregular uterine bleeding is a common symptom among women in the menopausal transition. Women commonly transition from having regular cycles to having irregular cycles before the final menstrual period. In late perimenopause, anovulation becomes more common, leading to skipped menstrual cycles. Low-dose oral contraceptive pills are effective in decreasing the amount of menstrual blood loss and improving menstrual cycle regularity. It is unclear whether menorrhagia is associated with normal perimenopausal hormonal changes. Studies to date have failed to correlate menorrhagia with hormonal levels and pathology within the uterus. Because of the common association between uterine pathology and menorrhagia, this is an important area for future studies. Vaginal dryness is a common symptom, particularly in late perimenopause. The association between vaginal dryness and low estrogen levels is clear. Estrogen-based hormone replacement therapy is effective in treating this symptom. Locally released estrogen therapy may be preferred over systemic therapy because of lower systemic estradiol levels, reduced side effects, and high efficacy. The long-term safety of these products, particularly in women with a history of breast cancer, requires more study. The prevalence of incontinence increases as women age, but it is unclear whether the menopausal transition is an independent risk factor. Incontinence is a frequent complaint among women in the menopausal transition. In postmenopausal women, hormone therapy (HT) appears to be ineffective in preventing or improving the symptoms of incontinence. Further study of HT, including locally applied estrogens for the common symptom of incontinence, are needed in women in the menopausal transition.

      Keywords

      The tissues of the genitourinary system are responsive to sex steroids. Therefore, it is not surprising that the hormonal fluctuations that characterize the menopausal transition lead to changes in the physiology of the reproductive tract and urinary system. These physiologic changes, in turn, can lead to new symptoms, resulting in physician consultation and treatment. This article reviews 3 common symptoms of the menopausal transition: abnormal uterine bleeding, vaginal dryness, and urinary incontinence. The prevalence, causes, and treatments of each symptom will be reviewed. Particular attention will be paid to the hormonal aspects of the pathophysiology and treatment of these symptoms.

      Abnormal uterine bleeding

      Menstrual cycles can be characterized by several measures, including cycle interval, duration of menstrual bleeding, and amount of blood lost. The time between the onset of menstrual periods (cycle interval) can be determined from menstrual calendars kept by women. In the reproductive years, most women have very predictable cycle intervals of 24 to 35 days.
      • Treloar A.E.
      Menstrual cyclicity and the pre-menopause.
      The duration of menstrual bleeding also can be determined from menstrual calendars and typically ranges from 4 to 6 days.
      • Wood C.
      • Larsen L.
      • Williams R.
      Menstrual characteristics of 2,343 women attending the Shepherd Foundation.
      The average volume of blood lost during menses is more difficult to measure. By carefully extracting hemoglobin from menstrual hygiene products, investigators have determined that the average volume of blood lost during menses is 30 mL. Blood loss >80 mL is considered abnormal because this amount of loss is frequently associated with the development of iron-deficiency anemia.
      • Hallberg L.
      • Högdahl A.M.
      • Nilsson L.
      • Rybo G.
      Menstrual blood loss—a population study variation at different ages and attempts to define normality.
      • Haynes P.H.
      • Hodgson H.
      • Anderson A.B.M.
      • Turnbull A.C.
      Measurement of menstrual blood loss in patients complaining of menorrhagia.
      Volume measurements are not clinically useful because their determination requires the task of collecting all menstrual hygiene products. Some researchers have touted menstrual pictograms, in which women estimate and record the blood concentration on hygiene products, as being highly correlated with actual measured blood loss
      • Higham J.M.
      • O’Brien P.M.A.
      • Shaw R.M.
      Assessment of menstrual blood loss using a pictorial chart.
      ; others have found essentially no correlation.
      • Reid P.C.
      • Coker A.
      • Coltart R.
      Assessment of menstrual blood loss using a pictorial chart a validation study.
      Defining menstrual blood volume lost in a cycle is difficult, but women are able to accurately report changes in menstrual blood loss perceived relative to their own personal history.

      Cycle irregularity in the menopausal transition

      In women of reproductive age, cycle intervals generally are predictable because of the cyclic occurrence of ovulation. Several longitudinal studies that used menstrual cycle calendars have demonstrated that women commonly transition from having regular cycles to more cycle irregularity before finally becoming postmenopausal, making irregular menstrual cycle intervals a normal finding in the perimenopausal years. For example, the Menstrual and Reproductive Health Research Program studied a total of 2,702 women for an average of 9.6 years, recording the experience of 35,000 person-years of menstrual history. These investigators noted that the first 6 years after menarche were characterized by a large variation in menstrual cycle intervals. Between the ages of 20 and 40 years women generally experienced more regular menstrual cycles with less variability. In the 8 years immediately before menopause (defined as the final menstrual period [FMP]), the interval between menstrual cycles again became much more variable (Figure 1).
      • Treloar A.E.
      Menstrual cyclicity and the pre-menopause.
      The median age of entry into the menopausal transition was 45.5 years; however, there was a wide range, with 50% of women entering the transition between the ages of 42.8 and 47.8 years. Although the characteristic finding was an increase in cycle intervals, some women noticed shorter cycle intervals in the menopausal transition. The important point is that there is some deviation from the prior “usual” pattern.
      Figure thumbnail gr1
      Figure 1Distribution of mean menstrual cycle intervals from 25,884 person-years of experience. (Reprinted with permission from Maturitas.
      • Treloar A.E.
      Menstrual cyclicity and the pre-menopause.
      )
      The menopausal transition is known to be a time of fluctuating hormone levels. These hormonal fluctuations may explain some of the menstrual cycle variability that is noted. Estradiol levels and inhibin-A levels are preserved at approximately the same concentration as found in reproductive-age women until very shortly before menopause. In the year preceding the FMP, there is a marked decrease in estradiol levels accompanied by a large increase in circulating gonadotropins, i.e., follicle-stimulating hormone and luteinizing hormone.
      • Burger H.G.
      • Dudley E.C.
      • Hopper J.L.
      • et al.
      The endocrinology of the menopause transition a cross-sectional study of a population-based sample.
      Longer cycle intervals are often associated with anovulatory cycles, and they are noted more often both in older perimenopausal women and in women with a greater body mass index.
      • Randolph J.F.
      • Sowers M.
      • Bondarenko I.V.
      • et al.
      Change in estradiol and follicle stimulating hormone across the early menopausal transition effects of ethnicity and age.
      In older perimenopausal women who are ovulatory, longer total cycle length is characterized by a longer follicular phase and a relatively shorter luteal phase.
      • Santoro M.
      • Lasley B.
      • McConnell D.
      • et al.
      Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition the Study of Women’s Health Across the Nation (SWAN) Daily Hormone Study.

      Treatment of irregular menstrual bleeding in the menopausal transition

      Women who are used to predictable menstrual bleeding patterns in the reproductive years can become concerned when they experience the more irregular menstrual periods that accompany the menopausal transition. Irregular and unpredictable menstrual bleeding can cause lifestyle and scheduling issues as well as evoking concerns about a possible undesired pregnancy. In addition, irregular bleeding may prompt physicians to obtain ultrasonographic evaluations or endometrial biopsies to rule out endometrial hyperplasia and cancer.
      Exogenous hormones are commonly used to regulate menstrual bleeding during the menopausal transition in women who do not have contraindications for this therapy. Use of a low-dose oral contraceptive pill has been shown to be effective for decreasing the amount of menstrual blood loss as well as improving menstrual cycle regularity in the menopausal transition.
      • Casper R.F.
      • Dodin S.
      • Reid R.L.
      Study Investigators
      The effect of 20 μg ethinyl estradiol/1 mg norethindrone acetate (Minestrin™), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes and quality of life in symptomatic perimenopausal women.
      Women taking birth control pills had an increased frequency of spotting during the first 12 weeks of pill use, but there was no difference between the 2 groups after 3 months of treatment. Women had the benefits of fewer hot flashes and an improved overall quality of life in addition to the contraceptive benefit of the pill.
      • Casper R.F.
      • Dodin S.
      • Reid R.L.
      Study Investigators
      The effect of 20 μg ethinyl estradiol/1 mg norethindrone acetate (Minestrin™), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes and quality of life in symptomatic perimenopausal women.
      Women who do not tolerate an oral contraceptive pill may benefit from alternative hormone therapies (HT) during the menopausal transition. One possibility is the use of HT at doses generally prescribed for the postmenopause (lower doses than in oral contraceptive pills). A disadvantage of this therapy is that the contraceptive efficacy of these lower doses of hormones has not been established. Use of long-lasting injectable progestins like depot medroxyprogesterone acetate (MPA) also may be effective for women in this age group. However, there is recent concern about long-term use of this therapy and the development of osteoporosis.
      • Berenson A.
      • Radecki C.
      • Grady J.
      • Rickert V.
      • Thomas A.
      A prospective controlled study of the effects of hormonal contraception on bone mineral density.
      In addition, women frequently experience spotting as a side effect of this medication. Because of the increased incidence of anovulatory cycles late in the menopausal transition leading to increased cycle length and unpredictable bleeding, some have advocated use of progestins (including MPA) given cyclically for 10 to 14 days a month. This therapy may be effective for women with very infrequent periods.

      Menorrhagia and the menopausal transition

      Menorrhagia is a common symptom, with up to 33% of women having this complaint at some time in their life.
      Market Opinion and Research International (MORI)
      Although irregular menstrual bleeding can be linked to hormonal changes of the menopausal transition, it is unclear whether or not menorrhagia is commonly associated with hormonal changes.
      Menorrhagia is associated with pathologic findings in the uterus, including endometrial polyps and uterine fibroids. Indeed, pathologic changes in the uterus are found in well over 50% of women presenting for ultrasonographic evaluation of menorrhagia.
      • Clevenger-Hoeft M.
      • Syrop C.H.
      • Stovall D.W.
      • Van Voorhis B.J.
      Sonohysterography in premenopausal women with and without abnormal bleeding.
      The prevalence of benign uterine lesions, including polyps and fibroids, peaks in women aged 40 to 50 years.
      • Clevenger-Hoeft M.
      • Syrop C.H.
      • Stovall D.W.
      • Van Voorhis B.J.
      Sonohysterography in premenopausal women with and without abnormal bleeding.
      • Marshall L.M.
      • Spiegelman D.
      • Barbieri L.R.
      • et al.
      Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.
      • Peterson W.F.
      • Novak E.R.
      Endometrial polyps.
      Thus, it is very difficult to separate menorrhagia due to normal perimenopausal changes from menorrhagia due to the development of benign uterine lesions.
      Recently, a high frequency of inherited bleeding disorders, including von Willebrand disease, has been discovered in older reproductive-age women with menorrhagia and a normal uterine cavity.
      • Kadir R.A.
      • Economides D.L.
      • Sabin C.A.
      • Owens D.
      • Lee C.A.
      Frequency of inherited bleeding disorders in women with menorrhagia.
      Therefore, platelet function assays and coagulation studies are indicated before surgery in women with refractory menorrhagia.
      One weakness of the longitudinal studies of the menopausal transition conducted thus far is the absence of correlation between menstrual bleeding complaints, hormonal levels, pathologic changes (e.g., polyps, fibroids, endometrial hyperplasia) within the uterus, and the presence of inherited bleeding disorders. Because of the well-known association between these pathologic entities with abnormal uterine bleeding, a comprehensive study of women with menorrhagia in the menopausal transition is an important area for future research.
      Although many of the same hormonal treatments used for control of cycle irregularity can be used for the management of menorrhagia, results are mixed. For example, oral contraceptive pills are known to reduce menstrual bleeding by 60%.
      • Shaw R.W.
      Assessment of medical treatments of menorrhagia.
      Nonsteroidal anti-inflammatory drugs also reduce both menstrual cramping and menstrual blood loss by about 20% to 40%.
      • Shaw R.W.
      Assessment of medical treatments of menorrhagia.
      Cyclic progestins have also been studied in women with menorrhagia. A recent prospective cohort study evaluated the effectiveness of 3 months of MPA 10 mg given for 10 to 14 days per month for treatment of menorrhagia. Only 65% of subjects completed the 3 months of therapy and, of this subgroup, only 57% expressed satisfaction with this therapy.
      • Richter H.E.
      • Learman L.A.
      • Lin F.
      • et al.
      Medroxyprogesterone acetate treatment of abnormal uterine bleeding factors predicting satisfaction.
      A systematic review concluded that cyclic administration of MPA was ineffective for treatment of menorrhagia.
      • Lethaby A.
      • Irvine G.
      • Cameron I.
      Cyclical progestogens for heavy menstrual bleeding.
      Another medical option for treating menorrhagia is the progestin-releasing intrauterine device (IUD), which can help women with menorrhagia while also providing contraception. The most commonly used progestin-releasing IUD is approved by the US Food and Drug Administration for contraception only. It releases levonorgestrel 20 μg/day for 5 years. After several months of intermittent spotting following insertion, a high percentage of women ultimately experience either very light periods or amenorrhea. The progestin-releasing IUD reduces menstrual blood loss more effectively than do oral progestins and oral contraceptive pills.
      • Farquhar C.M.
      Management of dysfunctional uterine bleeding.
      When medical options fail, many women with menorrhagia turn to surgical options for treatment, including hysterectomy, endometrial ablation, and uterine artery embolization. Discussion of these treatments is beyond the scope of the present article.

      Vaginal atrophy and dryness in the menopausal transition

      Estrogen stimulates the growth and development of vaginal epithelium, allowing it to remain thick, moist, and supple. Vaginal atrophy can occur with the dramatic reduction in estrogen that occurs just before the FMP; it is apparent clinically by the appearance of thin, pale, dry vaginal epithelium. The atrophic vagina lacks normal rugation, and the introital size is often reduced. Vaginal atrophy can be assessed objectively by obtaining vaginal wall cytology: the atrophic vagina will have a predominance of immature parabasal cells rather than the superficial squamous cells seen with estrogen stimulation.
      • Schaffer J.
      • Fantl J.A.
      Urogenital effects of the menopause.
      Vaginal pH is another method of assessing vaginal atrophy. In women of reproductive age, vaginal pH is <4.5; this low pH is thought to prevent colonization of the vagina with pathogenic bacteria. With decreased estrogen levels in the postmenopausal range, vaginal pH taken from the lateral vaginal wall has been noted to increase to between 6.0 and 7.5. The increase in pH seen with atrophy may lead to impaired protection against vaginal and urinary tract infections.
      • Caillouette J.C.
      • Sharp C.G.
      • Zimmerman G.J.
      • Roy S.
      Vaginal pH as a marker for bacterial pathogens and menopausal status.
      Estrogen therapy for atrophic vaginitis has been shown to reduce vaginal pH.
      • Notelovitz M.
      Estrogen therapy in management of problems associated with urogenital aging a simple diagnostic test and the effect of the route of hormone administration.
      Symptoms of vaginal atrophy include dryness, itching, vaginitis, and dyspareunia. Vaginal atrophy and dryness is a common symptom among women in the late menopausal transition. In a longitudinal study of 438 Australian-born women observed over 7 years, vaginal dryness was a complaint in 3% of regularly cycling women and in 4% of women in the early menopausal transition.
      • Dennerstein L.
      • Dudley E.C.
      • Hopper J.L.
      • Guthrie J.R.
      • Burger H.G.
      A prospective population-based study of menopausal symptoms.
      However by the late menopausal transition, 21% of women complained of vaginal dryness, and this percentage increased up to 47% in women who were 3 years postmenopausal.
      • Dennerstein L.
      • Dudley E.C.
      • Hopper J.L.
      • Guthrie J.R.
      • Burger H.G.
      A prospective population-based study of menopausal symptoms.
      The association between vaginal dryness and low estrogen levels is clear because estrogen levels decrease precipitously in the late menopausal transition.
      • Burger H.G.
      • Dudley E.C.
      • Hopper J.L.
      • et al.
      The endocrinology of the menopause transition a cross-sectional study of a population-based sample.
      Systemic administration of estrogen, including oral and transdermal preparations, has been shown to be effective in treating vaginal atrophy. Locally released estrogen—in the form of vaginal rings, estrogen-based vaginal creams, pessaries, and slow-release estradiol tablets—also has been shown to be effective.
      • Suckling J.
      • Lethaby A.
      • Kennedy R.
      Local oestrogen for vaginal atrophy in postmenopausal women.
      With local administration, lower doses of estrogen can be used for the treatment of vaginal atrophy. The advantages of local therapy include lower systemic estradiol levels, leading to fewer adverse effects such as endometrial stimulation, uterine bleeding, and breast tenderness. Lower systemic estradiol levels also may be advantageous for women who have been treated previously for estrogen-responsive cancers. Estrogen treatment results in rapid symptom relief, with significant improvement found after 2 weeks (Figure 2).
      • Riou J.E.
      • Devlin M.C.
      • Gelfand M.M.
      • Steinberg W.M.
      • Hepburn D.S.
      17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.
      Figure thumbnail gr2
      Figure 2Effect of 2 different forms of vaginal estrogen on vaginal dryness and symptom scores in menopausal women. (Reprinted with permission from Menopause.
      • Riou J.E.
      • Devlin M.C.
      • Gelfand M.M.
      • Steinberg W.M.
      • Hepburn D.S.
      17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.
      )
      A meta-analysis of locally administered estrogens has revealed no significant difference between the various types of local estrogen administration (e.g., tablets, creams, vaginal rings, or gels) in treatment of vaginal atrophy.
      • Suckling J.
      • Lethaby A.
      • Kennedy R.
      Local oestrogen for vaginal atrophy in postmenopausal women.
      It should be noted that the prospective randomized trials included in this systematic review were all relatively small, with the largest trial enrolling only 251 subjects. Few of the trials included a placebo group. Many times the choice of therapy depends on the ease and comfort of administration, with some women finding estrogen creams to be messier and more difficult to use.
      • Suckling J.
      • Lethaby A.
      • Kennedy R.
      Local oestrogen for vaginal atrophy in postmenopausal women.
      Vaginally administered estrogens are absorbed into the systemic circulation. Estrogen in creams is readily absorbed, particularly across immature atrophic mucosa. As the vaginal mucosa cornifies, absorption decreases.
      • Pschera H.
      • Hjerpe A.
      • Carlström K.
      Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17β and progesterone in postmenopausal women.
      When measured, estradiol levels generally remain in the postmenopausal range with use of commercially available products. However, because of systemic absorption, women using intravaginal estrogen preparations who have abnormal bleeding should have their endometrium sampled for the possibility of endometrial hyperplasia or cancer. The incidence of hyperplasia appears to be low (<10%), although most studies have only evaluated short-term use of transvaginal estrogen administration.
      • Vooijs G.P.
      • Geurts T.B.P.
      Review of the endometrial safety during intravaginal treatment with estriol.
      Clinically these products are often used without administering progestins, which commonly are used with systemic estrogen therapy for menopausal symptoms.
      Women with contraindications for estrogen use or who desire a “natural” alternative often use phytoestrogens for treatment of menopausal symptoms. Phytoestrogens have been studied for their effect on vaginal dryness and atrophy, and they appear to have no effect in most studies. For example, a recent double-blind, randomized, placebo-controlled trial evaluated the effect of daily use of isolated isoflavones 114 mg—the most common phytoestrogens in soya—on vaginal atrophy. This trial found no effect of phytoestrogens on subjective assessment of vaginal dryness or on the vaginal maturation index as assessed by vaginal wall cytology.
      • Nikander E.
      • Rutanan E.-M.
      • Nieminen P.
      • Wahlstrom R.
      • Ylikorkala O.
      • Titinen A.
      Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women.
      Nonhormonal products for vaginal dryness and difficulty with intercourse are commercially available. These moisturizers generally have rather short-term effects and are useful for sexual activity. Although they can improve vaginal dryness, they are not as effective as estrogen for long-term correction of this problem and they have no effect on maturation of the vaginal epithelium.
      • Bygdeman M.
      • Swahn M.L.
      Replens vs dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women.
      • Nachtigall L.E.
      Comparative study Replens versus local estrogen in menopausal women.

      Urinary incontinence in the menopausal transition

      There are several forms of urinary incontinence. The most common type is stress urinary incontinence, which is characterized by the symptom of involuntary loss of urine associated with coughing, sneezing, or physical activity. Urge urinary incontinence is characterized by loss of urine accompanied by a strong desire to void. Many women have a combination of problems (mixed urinary incontinence), including urinary frequency, urgency, and stress urinary incontinence.
      The prevalence of incontinence increases as women age.
      • Hannestad Y.S.
      • Rotviet G.
      • Sandvik H.
      • Hunskaar S.
      A community-based epidemiological survey of female urinary incontinence the Norwegian EPINCONT study.
      However, it is unclear whether the hormonal changes associated with the menopausal transition are independent risk factors for the development of incontinence. A prospective study of women’s symptoms across the menopausal transition revealed no increase in “urine control problems” as women progressed from having regular cycles to 3 years postmenopause. The prevalence of this complaint was approximately 15% for most points examined.
      • Dennerstein L.
      • Dudley E.C.
      • Hopper J.L.
      • Guthrie J.R.
      • Burger H.G.
      A prospective population-based study of menopausal symptoms.
      In addition, when evaluating the prevalence of “significant” incontinence, a large epidemiologic study from Norway found no significant increase at the ages when women can be expected to be in the menopausal transition (Figure 3).
      • Hannestad Y.S.
      • Rotviet G.
      • Sandvik H.
      • Hunskaar S.
      A community-based epidemiological survey of female urinary incontinence the Norwegian EPINCONT study.
      Figure thumbnail gr3
      Figure 3Prevalence of urinary incontinence in a population-based study. (Reprinted with permission from J Clin Epidemiol.
      • Hannestad Y.S.
      • Rotviet G.
      • Sandvik H.
      • Hunskaar S.
      A community-based epidemiological survey of female urinary incontinence the Norwegian EPINCONT study.
      )
      In contrast to the findings mentioned above, the Study of Women’s Health Across the Nation (SWAN)
      • Sampselle C.M.
      • Harlow S.D.
      • Skurnick J.
      • Brubaker L.
      • Bondarenko I.
      Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.
      found that perimenopausal status was a risk factor for the presence of any incontinence episodes and for the presence of moderate or severe incontinence compared with regularly cycling women (Table 1). Moreover, perimenopausal status was a stronger and more consistent predictor than age.
      • Sampselle C.M.
      • Harlow S.D.
      • Skurnick J.
      • Brubaker L.
      • Bondarenko I.
      Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.
      However, the study only included women in a small age range (42 to 52 years); it remains unclear whether hormonal changes or other aging phenomena contribute to the problem.
      Table 1Adjusted odds ratios for moderate/severe urinary incontinence among women reporting incontinence
      Risk FactorModerate/Severe Incontinence
      Adjusted Odds Ratio
      Adjusted for all variables in the model and site.
      95% Confidence Interval
      Perimenopausal status1.351.10–1.65
      Body mass index1.041.03–1.06
      Diabetes mellitus1.551.07–2.25
      Smoking1.381.04–1.82
      Ethnicity (white women = reference)
       African American0.880.67–1.16
       Chinese0.700.4–1.21
       Hispanic0.650.34–1.28
       Japanese1.130.68–1.88
      Reprinted with permission from Obstet Gynecol.
      • Sampselle C.M.
      • Harlow S.D.
      • Skurnick J.
      • Brubaker L.
      • Bondarenko I.
      Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.
      low asterisk Adjusted for all variables in the model and site.
      Incontinence is a common complaint in the menopausal transition. In SWAN, when severity of incontinence was assessed by questionnaire, 32% of respondents reported mild incontinence, 15% reported moderate incontinence, and 10% reported severe incontinence.
      • Sampselle C.M.
      • Harlow S.D.
      • Skurnick J.
      • Brubaker L.
      • Bondarenko I.
      Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.
      Furthermore, 11% of women in this study had mentioned the problem to a healthcare provider.
      Despite the lack of clear evidence for an increase in the prevalence of incontinence with menopause, some investigators have postulated that estrogen may contribute to continence mechanisms. However, it seems unlikely that HT, at least in the postmenopause, is helpful for the symptom of urinary incontinence. The Heart and Estrogen/Progestin Replacement Study (HERS)
      • Grady D.
      • Brown J.S.
      • Vittinghoff E.
      • Applegate W.
      • Varner E.
      • Snyder T.
      HERS Research Group
      Postmenopausal hormones and incontinence the Heart and Estrogen/Progestin Replacement Study.
      was a prospective, randomized, placebo-controlled trial evaluating the effects of conjugated estrogens 0.625 mg/day plus MPA 2.5 mg/day in women with coronary disease. In this study, 1,525 women reported incontinence defined as ≥1 episode of incontinence per week at baseline. Of these women, 768 were assigned to HT and 757 were assigned to placebo. Incontinence improved in 26% of women assigned to placebo compared with 21% of women assigned to HT. Incontinence worsened in 27% of women assigned to placebo and in 39% of women assigned to HT, a difference that was statistically significant (P = 0.001). This difference was evident by 4 months of treatment and was true for both stress and urge incontinence.
      • Grady D.
      • Brown J.S.
      • Vittinghoff E.
      • Applegate W.
      • Varner E.
      • Snyder T.
      HERS Research Group
      Postmenopausal hormones and incontinence the Heart and Estrogen/Progestin Replacement Study.
      Results from the Women’s Health Initiative (WHI) also suggest that HT in postmenopausal women is not helpful and may be harmful for the symptom of urinary incontinence. Hendrix and associates
      • Hendrix S.L.
      • Cochrane B.B.
      • Nygaard I.E.
      • et al.
      Effects of estrogen with and without progestin on urinary incontinence.
      reported that both conjugated estrogens alone and conjugated estrogens plus MPA increased the risk for the development of incontinence among women who were continent at the start of the study; furthermore, HT worsened the characteristics of incontinence among symptomatic women.
      • Hendrix S.L.
      • Cochrane B.B.
      • Nygaard I.E.
      • et al.
      Effects of estrogen with and without progestin on urinary incontinence.
      Postmenopausal HT increased the risk of developing stress incontinence to a greater degree than was seen for mixed or urge incontinence. These authors concluded that conjugated estrogens with or without progestins should not be prescribed for the prevention or relief of urinary incontinence.
      Whether HT begun in the menopausal transition affects the development or symptoms of incontinence is not known. In addition, locally applied estrogen in particular should be studied for its effects on incontinence. However, the best evidence to date does not suggest a role for HT for this common symptom of the menopausal transition.

      References

        • Treloar A.E.
        Menstrual cyclicity and the pre-menopause.
        Maturitas. 1981; 3: 249-264
        • Wood C.
        • Larsen L.
        • Williams R.
        Menstrual characteristics of 2,343 women attending the Shepherd Foundation.
        Aust N Z J Obstet Gynaecol. 1979; 19: 107-110
        • Hallberg L.
        • Högdahl A.M.
        • Nilsson L.
        • Rybo G.
        Menstrual blood loss—a population study.
        Acta Obstet Gynecol Scand. 1966; 45: 320-351
        • Haynes P.H.
        • Hodgson H.
        • Anderson A.B.M.
        • Turnbull A.C.
        Measurement of menstrual blood loss in patients complaining of menorrhagia.
        Br J Obstet Gynaecol. 1977; 84: 763-768
        • Higham J.M.
        • O’Brien P.M.A.
        • Shaw R.M.
        Assessment of menstrual blood loss using a pictorial chart.
        Br J Obstet Gynaecol. 1990; 97: 734-739
        • Reid P.C.
        • Coker A.
        • Coltart R.
        Assessment of menstrual blood loss using a pictorial chart.
        Br J Obstet Gynaecol. 2000; 107: 320-322
        • Burger H.G.
        • Dudley E.C.
        • Hopper J.L.
        • et al.
        The endocrinology of the menopause transition.
        J Clin Endocrinol Metab. 1995; 80: 3537-3545
        • Randolph J.F.
        • Sowers M.
        • Bondarenko I.V.
        • et al.
        Change in estradiol and follicle stimulating hormone across the early menopausal transition.
        J Clin Endocrinol Metab. 2004; 89: 1555-1561
        • Santoro M.
        • Lasley B.
        • McConnell D.
        • et al.
        Body size and ethnicity are associated with menstrual cycle alterations in women in the early menopausal transition.
        J Clin Endocrinol Metab. 2004; 89: 2622-2631
        • Casper R.F.
        • Dodin S.
        • Reid R.L.
        • Study Investigators
        The effect of 20 μg ethinyl estradiol/1 mg norethindrone acetate (Minestrin™), a low-dose oral contraceptive, on vaginal bleeding patterns, hot flashes and quality of life in symptomatic perimenopausal women.
        Menopause. 1997; 4: 139-147
        • Berenson A.
        • Radecki C.
        • Grady J.
        • Rickert V.
        • Thomas A.
        A prospective controlled study of the effects of hormonal contraception on bone mineral density.
        Obstet Gynecol. 2001; 98: 576-582
        • Market Opinion and Research International (MORI)
        MORI Women’s Health in 1990 [research study conducted on behalf of Parke-Davis Research Laboratories]. MORI, London, UK1990
        • Clevenger-Hoeft M.
        • Syrop C.H.
        • Stovall D.W.
        • Van Voorhis B.J.
        Sonohysterography in premenopausal women with and without abnormal bleeding.
        Obstet Gynecol. 1999; 94: 516-520
        • Marshall L.M.
        • Spiegelman D.
        • Barbieri L.R.
        • et al.
        Variation in the incidence of uterine leiomyoma among premenopausal women by age and race.
        Obstet Gynecol. 1997; 90: 967-973
        • Peterson W.F.
        • Novak E.R.
        Endometrial polyps.
        Obstet Gynecol. 1956; 8: 40-49
        • Kadir R.A.
        • Economides D.L.
        • Sabin C.A.
        • Owens D.
        • Lee C.A.
        Frequency of inherited bleeding disorders in women with menorrhagia.
        Lancet. 1998; 351: 485-489
        • Shaw R.W.
        Assessment of medical treatments of menorrhagia.
        Br J Obstet Gynecol. 1994; 101: 15-31
        • Richter H.E.
        • Learman L.A.
        • Lin F.
        • et al.
        Medroxyprogesterone acetate treatment of abnormal uterine bleeding.
        Am J Obstet Gynecol. 2003; 189: 37-42
        • Lethaby A.
        • Irvine G.
        • Cameron I.
        Cyclical progestogens for heavy menstrual bleeding.
        Cochrane Database Syst Rev. 2000; 2: CD00106
        • Farquhar C.M.
        Management of dysfunctional uterine bleeding.
        Drugs. 1992; 44: 578-584
        • Schaffer J.
        • Fantl J.A.
        Urogenital effects of the menopause.
        Baillieres Clin Obstet Gynaecol. 1996; 10: 401-417
        • Caillouette J.C.
        • Sharp C.G.
        • Zimmerman G.J.
        • Roy S.
        Vaginal pH as a marker for bacterial pathogens and menopausal status.
        Am J Obstet Gynecol. 1997; 176: 1270-1275
        • Notelovitz M.
        Estrogen therapy in management of problems associated with urogenital aging.
        Maturitas. 1995; 22: S31-S33
        • Dennerstein L.
        • Dudley E.C.
        • Hopper J.L.
        • Guthrie J.R.
        • Burger H.G.
        A prospective population-based study of menopausal symptoms.
        Obstet Gynecol. 2000; 96: 351-358
        • Suckling J.
        • Lethaby A.
        • Kennedy R.
        Local oestrogen for vaginal atrophy in postmenopausal women.
        Cochrane Database Syst Rev. 2003; 4: CD001500
        • Riou J.E.
        • Devlin M.C.
        • Gelfand M.M.
        • Steinberg W.M.
        • Hepburn D.S.
        17β-estradiol vaginal tablet versus conjugated equine estrogen vaginal cream to relieve menopausal atrophic vaginitis.
        Menopause. 2000; 7: 156-161
        • Pschera H.
        • Hjerpe A.
        • Carlström K.
        Influence of the maturity of the vaginal epithelium upon the absorption of vaginally administered estradiol-17β and progesterone in postmenopausal women.
        Gynecol Obstet Invest. 1989; 72: 204-207
        • Vooijs G.P.
        • Geurts T.B.P.
        Review of the endometrial safety during intravaginal treatment with estriol.
        Eur J Obstet Gynecol Reprod Biol. 1995; 62: 101-106
        • Nikander E.
        • Rutanan E.-M.
        • Nieminen P.
        • Wahlstrom R.
        • Ylikorkala O.
        • Titinen A.
        Lack of effect of isoflavonoids on the vagina and endometrium in postmenopausal women.
        Fertil Steril. 2005; 83: 127-142
        • Bygdeman M.
        • Swahn M.L.
        Replens vs dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women.
        Maturitas. 1996; 23: 259-263
        • Nachtigall L.E.
        Comparative study.
        Fertil Steril. 1994; 61: 178-180
        • Hannestad Y.S.
        • Rotviet G.
        • Sandvik H.
        • Hunskaar S.
        A community-based epidemiological survey of female urinary incontinence.
        J Clin Epidemiol. 2000; 53: 1150-1157
        • Sampselle C.M.
        • Harlow S.D.
        • Skurnick J.
        • Brubaker L.
        • Bondarenko I.
        Urinary incontinence predictors and life impact in ethnically diverse perimenopausal women.
        Obstet Gynecol. 2002; 100: 1230-1238
        • Grady D.
        • Brown J.S.
        • Vittinghoff E.
        • Applegate W.
        • Varner E.
        • Snyder T.
        • HERS Research Group
        Postmenopausal hormones and incontinence.
        Obstet Gynecol. 2001; 97: 116-120
        • Hendrix S.L.
        • Cochrane B.B.
        • Nygaard I.E.
        • et al.
        Effects of estrogen with and without progestin on urinary incontinence.
        JAMA. 2005; 293: 935-948