Updated Guidelines on Vasomotor and Genitourinary Symptoms of Menopause

The Royal Australian and New Zealand College of Obstetricians and Gynaecologists (RANZCOG) has recently published its Management of Vasomotor and Genitourinary Symptoms of Menopause (C-Gyn 9) guideline. This document is intended to support the assessment and treatment of the most common symptom groups experienced during this significant life transition.

Menopausal symptoms

Vasomotor symptoms (VMS) and genitourinary symptoms (GUS) are two of the most common groups of menopausal symptoms.

Vasomotor symptoms affect up to 75% of women and include hot flushes and night sweats. Women may experience symptoms ranging from sudden warmth and flushing to intense sweating that can disrupt sleep. These symptoms tend to predominate during perimenopause.

The most common GUS are vaginal and vulval dryness. Other symptoms may include dyspareunia, urinary urgency, dysuria, and recurrent urinary tract infections. In contrast to VMS, these symptoms tend to become more common and severe with advancing age.

Other menopausal symptoms that are not specifically addressed in this updated guideline include:

• Mood changes, depression and anxiety
• Joint aches and stiffness
• Changes in libido
• Cognitive difficulties (“brain fog”)
• Reduced quality of life

Management of vasomotor symptoms

Menopausal hormone therapy (MHT) is the first-line pharmacological treatment for women with bothersome vasomotor symptoms who do not have contraindications. It is available in a number of different formulations, including oral tablets and transdermal patches, gels, and sprays. Transdermal oestrogen is associated with a lower risk of venous thromboembolism (VTE) and gallbladder disease than oral oestrogen.

Women with a uterus require both oestrogen and progestogen to protect the endometrium, while women who have had a hysterectomy can have oestrogen only therapy. The guidelines recommend starting with a low dose and adjust according to symptom control. Annual review is recommended.

There are many contraindications and precautions for MHT, including:

• Known or suspected hormone-dependent cancers (including breast and endometrial cancer)
• Coronary heart disease, stroke, myocardial infarction or thromboembolism
• Unexplained vaginal bleeding
• Untreated endometrial hyperplasia
• Active or chronic liver disease
• Severe uncontrolled hypertension
• High inherited thromboembolic risk
• Porphyria

Treatment decisions should be individualised based on the patient’s risk profile. Non-hormonal medicines may be considered for patients who cannot use MHT and for patients who prefer to avoid MHT. Options include:

• Fezolinetant
• Selective serotonin reuptake inhibitor (SSRI)
• Serotonin–norepinephrine reuptake inhibitor (SNRI)
• Gabapentin
• Oxybutynin

Fezolinetant is a relatively new medication for the treatment of VMS. It is a selective neurokinin-3 (NK₃) receptor antagonist that modulates neuronal activity in the thermoregulatory centre of the hypothalamus. Activity in this area is normally inhibited by oestrogen. Declining oestrogen levels during menopause leads to increased signalling in this area of the brain, contributing to the development of VMS.

The usual dose is 45 mg taken once daily with or without food. Fezolinetant is primarily metabolised by CYP1A2. Concomitant use of moderate or strong CYP1A2 inhibitors (e.g. ethinyl oestradiol-containing contraceptives, ciprofloxacin, fluvoxamine) is contraindicated. It is also contraindicated in patients with moderate to severe chronic hepatic impairment or severe to end-stage renal impairment.

Clinical studies have shown that fezolinetant reduces both the frequency and severity of vasomotor symptoms. However, the evidence is generally more robust for reductions in symptom frequency than severity.

Dosing considerations for other non-hormonal options are shown in Table 1.

Table 1. Summary of non-hormonal options for VMS (adapted from Management of vasomotor and genitourinary symptoms of menopause Quick Reference Guide)

Some women may prefer non-drug options, such as hypnosis or exercise and physical activity.

Exercise may not directly reduce hot flushes but has proven benefits for a range of issues including:

• Mental health
• Sleep quality
• Muscle strength
• Bone health
• Overall wellbeing.

Management of genitourinary symptoms

Vaginal oestrogen is a first line option for GUS. It is available as creams, pessaries, tablets or rings. Unlike systemic MHT, low-dose vaginal oestrogen has minimal systemic absorption and is often continued long term for persistent symptoms. Vaginal dehydroepiandrosterone (DHEA) may be considered as an alternative for patients with vulvovaginal dryness and dyspareunia.

Summary

The most common symptoms of menopause are hot flushes, night sweats, and genitourinary symptoms such as vaginal dryness. Menopausal hormone therapy is the most effective treatment for VMS, while local vaginal oestrogen or vaginal DHEA are effective options for GUS. Treatment should be individualised and reviewed regularly.

Additional resources:

• Quick reference guide for clinicians (includes prescribing tables)
• Patient information pamphlet (assist patients to understand the treatment options available and make informed decisions)
• Podcast episode (summarises the key takeaways from the guideline)