7.1 Menopausal Symptoms

It is important to remember that, with the exception of early/premature menopause, reproductive aging occurs concurrently with somatic aging and symptoms experienced by women may relate to the normal aging process rather than menopause.  Longitudinal studies demonstrate that only vasomotor symptoms (including hot flushes and night sweats), symptoms of genitourinary  atrophy and sleep disturbance have a consistent association with oestrogen deficiency . However, a variety of other symptoms may be experienced by peri- and post-menopausal women as reported by participants in the longitudinal Melbourne Women’s Midlife Health Project (see Figure: Symptoms in Australian women). Hot flushes, night sweats vaginal dryness, and insomnia increase in severity across the menopause transition whereas breast tenderness decreases. Multiple factors influence menopausal symptomatology  (see Table: Factors influencing menopausal symptoms).  A cross cultural study of four ethnic groups in Sydney reported a lower prevalence of symptoms in Indian and Chinese women compared with Arabic women or the general Caucasian population. Women with premature/ early menopause experience the same spectrum of symptoms as women with natural age menopause however, symptom frequency and severity are increased.

Table: Factors influencing menopausal symptoms.

7.1.1 Hot flushes

A hot flush may be defined as a subjective sensation of heat localized to the upper part of the body (chest, arms and head) with a mean duration of 3-4 minutes and associated with objective signs of cutaneous vasodilatation and a subsequent drop in core body temperature. Hot flushes are frequently accompanied by palpitations, and anxiety. The pathophysiology of hot flushes remains unclear; however, altered serotonin and noradrenalin levels secondary to oestrogen withdrawal  are postulated to result in changes in the hypothalamic thermoregulatory set point resulting in the hot flush sensation. The reported prevalence of hot flushes varies (related to population differences or study limitations); affecting  up to 85% of peri- and 66% of postmenopausal women, with severe symptoms observed in 10-20% of women. Hot flushes usually commence during the menopausal transition with the highest frequency reported around the final menstrual period then declining during the post- menopausal phase. The mean duration of vasomotor symptoms in the Melbourne Women’s Midlife Health Project cohort was 5.2 years with 23% of women reporting flushing at year 13 of follow-up.

7.1.2 Urogenital symptoms

Urogenital symptoms are common, affecting 50% of postmenopausal women; however, women are often reluctant to volunteer these symptoms. Vaginal changes secondary to oestrogen deficiency include thinning, shortening and narrowing of the vagina with decreased elasticity, blood flow, and secretions. Increase in vaginal pH from acid to more alkaline alters vaginal microbial flora with predisposition to urinary tract infections.  Vaginal atrophy results in symptoms of vaginal dryness or discomfort, pruritis and dyspareunia. In contrast to vasomotor symptoms, atrophic vaginitis is more prevalent during the post-menopausal period and is usually progressive. Smokers and women who are sexually inactive or have never given birth vaginally have an increased risk of vaginal atrophy. Post-menopausal atrophy of urethral and bladder mucosa may result in urinary urgency/ frequency, increased risk of cystitis and incontinence. 

7.1.3 Breast cancer

Women diagnosed with breast cancer may experience menopausal symptoms secondary to (i) diagnosis of breast cancer occurring concurrently with natural menopause, (ii) withdrawal of hormone replacement therapy following breast cancer diagnosis (iii) menopause induced by breast cancer treatment (GnRH agonist therapy, oophorectomy or chemotherapy) and (iv) side effects of adjuvant therapy including tamoxifen and aromatase inhibitors (see Table: Side effects of Aromatase inhibitors and Tamoxifen). Vasomotor symptoms, reported in up to 80% of women (particularly younger women), are more severe and frequent compared to women without breast cancer.  Up to 20% of breast cancer patients cease/ consider ceasing endocrine therapy due to menopausal symptoms.

Table: Side effects of Aromatase inhibitors and Tamoxifen.

Figure: Symptioms reported by Australian women

7.2 Sexual dysfunction

Sexual dysfunction occurs when the woman “perceives that she has an inability to experience sex as she would wish” (thus causing distress) and encompasses problems with desire/ libido, arousal, orgasm and sexual pain (including dyspareunia and vaginismus). Sexual dysfunction is common in the Australian general community with 50% of women reporting lack of interest and 20-27% reporting pain or lack of pleasure with sex. In addition, data from the Melbourne Women’s Midlife Health project indicate a significant decline in sexual functioning across the natural menopause transition; the percentage of women with sexual dysfunction increasing from 42 to 88%. The decline in sexual functioning across the natural menopause transition correlates with falling oestradiol (but not testosterone) levels; however, the relationship between hormone levels and sexual dysfunction remains unclear.  Women are often reluctant to disclose concerns regarding sexual dysfunction and may present with a variety of non-specific symptoms; direct questioning may be necessary. Sexual dysfunction is multifactorial and results from the interplay of both physiological factors  (for example, age, illness, menopausal status,effect of medication)  and psycho-social functioning ( for example, cultural influences, education, self-image, partner/ relationship issues, concurrent depression and anxiety) (see Table: Risk factors associated with sexual dysfunction). The four factors correlating best with sexual function are a woman’s psychological health, her feelings for her partner, her expectations regarding the relationship’s future and her past sexual experience

Women with breast cancer, particularly younger women who develop early/ premature menopause, experience greater rates of sexual dysfunction compared with the general community. Dyspareunia related to vaginal atrophy leading to decreased sexual desire is the commonest symptom of sexual dysfunction reported in young  women  with breast cancer.

Table: Risk factors associated with sexual dysfunction

7.3 Androgen deficiency

Androgen deficiency may be due to disorders affecting the hypothalamus/ pituitary, adrenals, ovaries or factors causing an increase in sex hormone binding globulin and therefore affecting bioavailable testosterone. The causes of androgen deficiency  in women are varied (see Table: Causes of Androgen deficiency in women) The female androgen insufficiency syndrome (Bachmann et al., Princeton Consensus statement 2001) comprises the key symptoms of reduced libido, diminished well being and lowered mood in the setting of a low bioavailable testosterone and adequate oestrogen levels. Hypoactive sexual desire disorder is defined by DSM IV in both men and women as persistently recurrent deficient (or absent) sexual fantasies and desire for sexual activity which causes marked distress or interpersonal difficulties and is not due to another mental disorder, medical condition or drug. However, there is a lack of sensitive and reliable testosterone assays (see Measurement of testosterone in women) and normative data with poor correlation between symptoms and androgen levels. Short term clinical trials of testosterone (often using supraphysiogical doses) have demonstrated improvement in aspects of sexual function, cognitive function and bone mineral density in oestrogen replete women. However, there is insufficient evidence to support the generalised use of testosterone by women currently. The Endocrine Society guidelines (2006) recommend against making the diagnosis of androgen deficiency in women due to “inadequate indication and lack of long term safety data” with a call for additional research.

Table : Causes of Androgen deficiency in women

SHBG- Sex hormone binding globulin

7.4 Depression/ Mood disorders

Anxiety and depression are the leading causes of burden of disease in Australian women (Australian Institute of Health and Welfare, 2003). The menopause transition may be a time of psychological vulnerability for some women; however, the evidence is conflicting as to whether natural perimenopause/ menopause is associated with an increased risk of de novo depression although depressive symptoms are commonly reported (see Figure: Symptoms reported by Australian women ). Observational data suggest that anxiety symptoms increase during the menopausal transition independently of depression and vasomotor symptoms. Studies also indicate an increased risk of depression and anxiety with surgical menopause and premature/ early menopause. Mixed results are observed regarding the effect of HRT on mood and behavior.

7.4   Early/premature menopause  

The clinical presentation of premature menopause (PM) is variable (see Early Menopause Website Table: Clinical Presentation of PM). Menstrual disturbance is the most common reported presenting symptom; however, there is no particular menstrual pattern which could indicate PM. A similar spectrum of menopausal symptoms (see 7.1 Menopausal symptoms) is observed although they are frequently more severe than those experienced by women with natural menopause. Vasomotor symptoms are present in  over 50% of women and may accompany menstrual disturbance or be associated with regular menses.

References

• Bachmann GA, Bancroft J et al., Female androgen insufficiency: The Princeton consensus statement on definition, classification and assessment Fertil Steril (2001) 77: 665-670
• Begg S, Vos T, et al. The burden of disease and injury in Australia in 2003. Australian Institute of Health and Welfare. http://www.aihw.gov.au/publications/index.cfm/title/10317
• Dennerstein L, Dudley EC  et al., A prospective population-based study of menopausal symptoms Obstet Gynecol (2000) 96: 351-358.
• Dennerstein L, Lehert P et al., Sexuality.  American Journal of Medicine (2005) 118 Suppl 12B:59-63.
• Androgen therapy in women guideline taskforce. Androgen therapy in women: An Endocrine Society clinical practice guideline.  J Clin Endocrinol Metab. (2006) 91: 3697-3716
• Hickey M, Saunders C et al., Practical guidelines for assessing and managing menopausal symptoms after breast cancer. Ann Oncol (2008) 19:1669-1680.
• Rivera-Woll Lm, Papalia M, et al., Androgen insufficiency in women: diagnostic and therapeutic implications. Hum Reprod Update (2004) 10:421-432.
• Soules MR , Sherman S et al., Executive summary: Stages of reproductive aging workshop (STRAW). Fertil Steril. (2001) 76:874-878.
• Somboonporn W, Bell RJ, Davis SR. Testosterone for peri and postmenopausal women. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD004509. DOI: 10.1002/14651858.CD004509.pub2.

 8. Diagnosis

Content updated December 2010