Consensus statement for non-estrogen-based treatments for menopausal symptoms

Introduction

Non-hormonal and hormonal strategies will be discussed. Complementary or alternative therapies are covered in the consensus statement ‘Alternative Therapies’. Non-hormonal therapies are useful particularly for women with estrogen-dependent disease such as breast^1–3 and endometrial cancers.

Hot flushes

Hot flushes and night sweats are the most common menopausal symptoms, and there is evidence they may last for several years. ⁴ Several non-estrogen agents have been used for symptom control although none are as effective as estrogen.^5,6 The non-hormonal therapies that have been tested in randomised placebo-controlled trials and shown to be effective include paroxetine, fluoxetine, citalopram and escitalopram, venlafaxine and desvenlafaxine, and gabapentin and pregabalin.^2,6

Selective serotonin reuptake inhibitors (SSRIs)/licensed class antidepressants SSRIs such as paroxetine, fluoxetine, citalopram and escitalopram all have been studied for reduction in vasomotor symptoms. The SSRI with the best evidence is paroxetine ⁷ with more recent studies assessing efficacy for citalopram and escitalopram.^8–12 Some SSRIs are known to have a strong potency for inhibiting cytochrome P450 (CYP) 2D6, an enzyme that is important in the metabolism of many drugs including tamoxifen. ¹³ SSRIs such as paroxetine and fluoxetine are known to inhibit CYP2D6 and therefore should be avoided in patients who are concomitantly taking tamoxifen.^2,13 Citalopram has weak inhibitory potency and can be taken with tamoxifen.^13,14 Paroxetine is the SSRI with the best evidence for efficacy^6,7 and is the SSRI for choice for patients not taking tamoxifen.¹⁵ Paroxetine is effective at a dose of 10 mg daily. Higher doses are not associated with improved control of flushes although the more usual dose of 20 mg may be used if an antidepressant effective is also desired. ¹⁶ These SSRIs have been evaluated in short-duration trials for menopause symptom control. All SSRI s may have an adverse effect on libido.

Urogenital problems

Vulvar and vaginal atrophy is an unremitting medical condition experienced by many postmenopausal women.^26,27 Symptoms include dyspareunia (pain with intercourse), vaginal dryness and irritation and may affect sexual activities, relationships and activities of daily life. The standard effective treatment is vaginal estrogen therapy. ²⁷ However, in women who do not wish to use local estrogen therapy, vaginal moisturisers are an option that can provide long-term relief of vaginal dryness. These may contain a bioadhesive polycarbophil-based polymer which attaches to mucin and epithelial cells on the vaginal wall and retains water. ReplensMD is an example of a vaginal moisturiser available on prescription in the UK, and is used at least twice weekly. Patients often notice a shedding process shortly after starting treatment. A plethora of vaginal lubricants are also available. Lubricants usually consist of a combination of protectants and thickening agents in a water soluble base. Some moisturisers and lubricants can be prescribed, and others are available online or through health stores and pharmacies.

A Swedish study on sexual dysfunction in women with breast cancer and on adjuvant endocrine therapy found that women who were on aromatase inhibitors had insufficient lubrication and dyspareunia, whereas tamoxifen-treated patients reported dyspareunia more frequently. ²⁸ These women would benefit from vaginal moisturisers and lubricants.

Lack of sexual desire

Forty percent of postmenopausal women report loss of sexual desire.^29–31 All women should be offered a holistic management plan. This should include options to help with relief of localised vaginal symptoms if present, referral for counselling if required, with assessment for need for systemic hormonal treatment based on an individualised risk/benefit evaluation. Psychosexual therapy has a proven success rate. ³⁰ Several studies have shown the benefit of testosterone therapy, mainly in surgical or postmenopausal women using estrogen.^32–35 In the UK, the only licensed preparations for women are subcutaneous implants or pellets which are becoming difficult to source. Testosterone patches for hysterectomised women who are also taking estrogen replacement therapy are no longer available. Testim ³⁶ and testogel, ³⁷ licensed for male hypogonadism, are sometimes used off-licence for women. The advice given to women is that they should make the 5 g sachet of testogel or the 5 g tube of testim last seven days. As this poses a challenge for accurate dosing, many practitioners will not prescribe these regimens for women. Tibolone,^38,39 a gonadomimetic with estrogenic, progestogenic and weak androgenic activity is licensed as a hormone replacement treatment for use in postmenopausal women with menopausal symptoms. Its androgenic activity may improve libido, energy levels and general well-being.^30,31,39

Summary practice points

Non-hormonal options are available for reducing vasomotor symptoms in women who cannot take estrogen but are less effective.