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Is it Menopause?

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By Dr. Jane Lee

Learning Objectives 

  • After completing this activity pharmacists should be able to:

  • Recall the definitions of perimenopause and menopause, and the changes in the body that occur at a biological level;

  • Outline the symptoms and signs of menopause that women may experience, as well as understand the impact of these symptoms;

  • Recognise that there are other conditions that may have similar symptoms to menopause;

  • Highlight the pharmacological and non-pharmacological treatments that are available for menopause.

CPD Accreditation

This activity has been accredited for 1 hour of Group One CPD (or 1 CPD credit) suitable for inclusion in an individual pharmacist’s CPD plan, which can be converted to 1 hour of Group Two CPD (or 2 CPD credits) upon successful completion of relevant assessment activities.

Accreditation Number: A2312ACP1

Expiry: 30/11/2025

Assessment Questions

This article has been re-printed in Australasian Pharmacy Magazine. You can access assessment questions via the College Learning Management System here. Please note: You must have an account with the College to access. You can join here. 

Introduction

Menopause is a natural biological process that signifies the cessation of a woman’s reproductive ability. It is characterised by a range of physical and psychological changes, often accompanied by a wide spectrum of different symptoms1. The World Health Organization (WHO) describes the importance of understanding menopause as one point in a continuum of life stages, and recognises that menopause, and its transitional phase, perimenopause, can have a significant impact on a woman’s physical, emotional and mental health2. There are several common concerns and gaps in knowledge associated with this stage of a woman’s life, and this article explores the management of menopause by pharmacists, including understanding the biological changes that occur in the body during menopause, diagnosing menopause and managing its symptoms. 

Perimenopause and menopause

The term ‘perimenopause’ describes the transitional period, usually between 4 - 8 years, leading up to menopause and for the first 12 months after the final menstrual cycle1, 3. Menopause is defined by the final menses a woman experiences and after 12 months of amenorrhoea, a woman is considered ‘post-menopausal’3.

Menopause is a universal experience for women, affecting all women who reach a certain age. A variety of factors can influence the age at which menopause occurs in women, including the age of onset of menstruation, the use of oral contraceptives, the number of pregnancies experienced, Body Mass Index (BMI), smoking, alcohol consumption, physical activity and genetic factors4, 5. While the mean age of menopause is typically around 51 years, natural menopause occurs between the ages of 45 and 56 years in 90% of women6, 7. Menopause can occur earlier in a small percentage of women, due to a condition known as ‘premature ovarian insufficiency’ (POI), which is characterised by the loss of ovarian function8. POI may occur spontaneously (in 1-2% of women) or as a secondary result of surgical intervention in women with endometriosis, high risk of ovarian or endometrial cancer or in those undergoing chemotherapy or radiotherapy3. 

Biological changes that occur during menopause 

As women age, natural physiological changes in the body cause a reduction in the number of ovarian follicles, resulting in a decreased response to the effects of Follicle-Stimulating Hormone (FSH)9. Consequently, the lack of Luteinising Hormone (LH) surge prevents ovulation, leading to diminishing estrogen production9. This cascade of hormonal changes disrupts the hypothalamic-pituitary-ovarian axis, affecting the development of the endometrial lining, which leads to increasingly irregular menstrual cycles, until the eventual cessation of menstruation occurs altogether9.

Symptoms of Menopause

Menopause is associated with a wide range of physical and psychological symptoms, primarily driven by the fluctuation and eventual decline in estrogen levels within the body. Figure 1 summarises the key symptoms and changes that occur during this unique stage of life. The manifestation of menopausal symptoms varies significantly between individual women, reflecting diverse experiences in the intensity and duration of symptoms. Approximately 1 in 5 women report no menopausal symptoms at all1. 

Vasomotor Symptoms 

The Australasian Menopausal Society describes a hot flush as a ‘subjective sensation of extreme heat associated with objective signs of cutaneous vasodilation and a subsequent drop in core body temperature’1. Hot flushes and night sweats are the most commonly reported symptoms of the menopausal transition and are experienced by up to 80% of women, with 25% of these women being severely affected10, 11. While symptoms may resolve within 2-5 years, more recent studies report the average duration of symptoms lasting between 7-10 years1, 12, 13. Vasomotor symptoms during menopause are associated with poor sleep quality, depressive moods and decreased quality of life, adversely affecting a woman’s relationships, work and family life and personal wellbeing1, 14, 15. 

Genitourinary Symptoms

Genitourinary symptoms associated with menopause, also referred to as ‘Genitourinary Syndrome of Menopause’ (GMS) or ‘vulvovaginal atrophy’, increase in incidence with age. Yet a reluctance to discuss these symptoms with  health care providers often cause women to endure these symptoms silently1. Symptoms can include vaginal dryness and burning, irritation, decreased libido and lubrication during sexual activity, dysuria, nocturia, urinary incontinence and an increased risk of urinary tract infections3, 16. These symptoms can greatly impact quality of life and self-esteem, especially in women who are sexually active. Pharmacists are encouraged to actively discuss GSM symptoms with patients and reassure women that these symptoms are natural and common, reminding women to seek treatment options from their doctor if symptoms are bothersome. 

Psychological and Cognitive Symptoms 

The combination of the complex hormonal changes and associated vasomotor/genitourinary symptoms and sleep deprivation can lead to changes in mood, anxiety, irritability, memory and concentration1, 3, 17. Studies also report a 50% decrease in the levels of serotonin, subsequent to the decline in estrogen levels circulating the body18, 19. These changes increase the risk of mental health disorders in menopausal women, particularly in those with a history of depression, anxiety, or other mood disorders.  

Dermatological Symptoms 

Estrogen plays a central role in the regulation of skin physiology, targeting keratinocytes, fibroblasts, hair follicles and sebaceous glands and improves wound healing and immune responses20. Therefore, estrogen insufficiency during menopause leads to dermatological changes including skin thinning (atrophy), acceleration of ageing and reduced collagen production, decreased elasticity, increased dryness, and reduced vascularity20, 21.  The protective function of the skin becomes compromised, which contributes to impaired wound healing20, 21. Other dermatological symptoms can include hair loss, pigmentary changes, pruritis (itching) and formication (feeling of ants crawling on the skin)1, 20. 

Bone and Muscle Changes

Estrogen plays a crucial role in the regulation of bone and skeletal muscle remodelling and growth, and therefore, the menopausal transition is associated with decreased bone density/strength and sarcopenia (age-related loss of muscle mass and strength)22, 23. The risk of osteoporosis is elevated in post-menopausal women, and the Australasian Menopause Society reports that one in three women over the age of 50 experiences a fragility fracture, and recommends all menopausal women have a clinical osteoporosis risk assessment1. Laird et al24 suggest a key role for pharmacist interventions in osteoporosis management, by actively raising public awareness, identifying individuals for screening and diagnosis and assisting with treatment uptake and improving adherence.

Metabolic Changes 

The metabolic changes resulting from estrogen insufficiency during menopause can impact a woman’s metabolism and overall health. Many women experience weight gain during menopause, particularly around the abdominal region. This weight gain can be attributed to several factors, such as decreased physical activity, changes in nutrition and a slower metabolic rate25. Furthermore, this life stage can be associated with alterations in blood lipid profiles, including increased levels of low-density lipoprotein (LDL) cholesterol and decreased levels of high-density lipoprotein (HDL) cholesterol25, 26. Some women may develop insulin resistance during menopause, which can lead to impaired glucose metabolism and an increased risk of developing Type II Diabetes Mellitus25. In combination, these metabolic changes can lead to an increase in cardiovascular risk and account for cardiovascular disease (CVD) being the leading cause of death in postmenopausal women7, 27-29.  

Figure 1. Overview of menopausal symptoms. 

Diagnosing Menopause

A diagnosis of menopause can often be confirmed based on a woman’s menstrual pattern, the presence of menopausal symptoms, and age3. For women older than 45 years, measurement of hormonal blood levels is not routinely required to confirm a diagnosis of menopause1, 3. Rather, the Australasian Menopause Society recommends the use of a symptom score sheet known as the Modified Greene Scale to assist with diagnosis, as this tool can help reveal other unreported menopausal symptoms1, 30. 

In cases where menstrual bleeding patterns are unreliable or difficult to interpret, such as in women who have had a hysterectomy or endometrial ablation, or who have amenorrhoea induced by progestogen-only contraception, serum levels of FSH, LH and estradiol may assist clinicians in confirming a diagnosis of menopause1, 3. In response to the declining levels of estrogen and reduced sensitivity of the ovaries during the menopausal transition, the pituitary gland increases production of FSH and LH via a negative feedback cycle. Hence, elevated levels of serum FSH and LH, coupled with a significant decrease in estrogen levels, are used as diagnostic markers for menopause3, 9. These tests are also used for the assessment of younger women who exhibit signs of amenorrhoea due to POI or early menopause3. It should be noted that serum FSH, LH and estrogen concentrations should not be measured if any estrogen-containing treatment (e.g. menopausal hormonal therapy (MHT), combined oral contraception) has been taken within 4 weeks3. These levels are not influenced by progestogen-only contraception, with the exception of depot medroxyprogesterone3. 

Anti-Mullerian Hormone (AM H) is a hormone produced by developing ovarian follicles and can serve as a marker for ovarian function31. While some research suggests reduced AMH levels can be used as a predictor of the onset of menopause, current guidelines do not recommend the measurement of serum AMH levels, except under specialist instruction, due to its significant cost and variability in its sensitivity3, 32. 

Differential Diagnoses

In women 45 years of age or older, a diagnosis of menopause can often be clinically made based on the presentation of menopausal symptoms. In younger women, it is necessary to exclude other conditions that can mimic or be mistaken for symptoms of menopause. Some examples are discussed below:

  • Polycystic Ovarian Syndrome (PCOS): can cause irregular periods, hot flushes, changes to lipid and metabolic profiles33

  • Thyroid disorders: symptoms of hypothyroidism include fatigue, mood swings, weight gain, irregular menstrual cycles, while hyperthyroidism can cause symptoms such as hot flushes, palpitations and insomnia34

  • Pregnancy: the most common cause of amenorrhoea and other symptoms such as fatigue and breast tenderness

  • Some medications: some medications such as antidepressants (i.e. SSRIs) and certain cancer treatments can cause hot flushes1 

  • Depression, stress and anxiety: can lead to symptoms like hot flushes, mood swings and sleep disturbance that can be misattributed to menopause15 

  • Other gynaecological conditions: fibroids, endometriosis and adenomyosis can cause irregular menstrual patterns and pelvic pain that can mimic the menopausal transition1 

  • Other hormonal disorders: consider the possibility of other disorders such as pituitary dysfunction including hyperprolactinemia, Sheehan syndrome (necrosis of the anterior pituitary) and pituitary adenoma, and adrenal gland disorders such as congenital adrenal hyperplasia and Cushing’s syndrome9

To exclude these differential diagnoses, a doctor should conduct a thorough medical history and physical examination, blood tests including serum hormone levels and thyroid function tests and imaging studies as necessary. Pharmacists play an important role in discussing symptoms with patients and referring patients to their GP to obtain an accurate diagnosis and appropriate management. 

Management of Symptoms

The goals of menopausal management are to help alleviate symptoms, improve quality of life, and reduce the risk of osteoporosis for women undergoing this life stage transition. Management options include both pharmacological treatments as well as lifestyle modifications.

Pharmacological Treatments

Hormonal Replacement Therapy (HRT)

Hormonal Replacement Therapy (HRT), also sometimes referred to as Menopausal Hormone Therapy (MHT), is the mainstay treatment for menopause, and is most effective for vasomotor symptoms (hot flushes and night sweats) and some urogenital symptoms, and consequently, may also improve other symptoms including sleep disturbance, mood swings, depression and tiredness3, 35. HRT also plays a key role in the prevention and management of osteoporosis and the preservation of an advantageous lipid profile3, 9. HRT should be used at the lowest effective dose for the shortest duration possible and pharmacists and GPs are encouraged to have regular discussions with patients to monitor patient response, reviewing the ongoing need for therapy. 

Systemic HRT includes estrogen-only options, estrogen and progestogen combinations, as well as other forms of systemic hormone regulators such as tibolone and conjugated estrogens with bazedoxifene3 (see Table 1 for the types of systemic HRT and appropriate subgroups for treatment). A variety of different dosage forms (i.e. tablets, creams, patches) and different modalities (i.e. continuous verses cyclical) are available, and selection should be tailored to individual patient needs. Before prescribing, a thorough history and clinical examination is conducted and mammograms, breast checks and cervical screening should be up to date in all women over 50 years with any unexplained bleeding investigated1. Table 2 provides examples of the types of preparations currently available Australia. 

Intravaginal estrogen therapy is delivered by pessaries or creams and is the most effective treatment option for urogenital symptoms such as vaginal dryness, irritation, dyspareunia, urinary frequency, dysuria and nocturia3. They can be used alone or in combination with systemic HRT or non-hormonal treatment options such as vaginal lubricants. 

Contraindications for HRT

Contraindications for HRT use include undiagnosed vaginal bleeding, a history of breast or endometrial cancers, acute cardiovascular or thromboembolic events. Specialist advice should be sought for individuals who have the following risk factors3, 9:

  • increased risk of VTE (including smoking, obesity, and thrombophilia);

  • previous stroke or myocardial infarction (MI);

  • uncontrolled hypertension;

  • > 60 years of age;

  • increased familial risk of breast cancer;

  • history migraines with aura;

  • severe liver disease;

  • endometriosis;

  • porphyria or systemic lupus erythematosus (SLE).

Risk of Harms Associated with HRT 

Current guidelines suggest that the benefits of systemic HRT outweigh the risks in most healthy peri- and postmenopausal women < 60 years of age. Estrogen-only preparations are known to increase the risk of endometrial cancer, and therefore, should only be used in women who have had a total hysterectomy. Oral and transdermal HRT are associated with an increased risk of breast cancer; this risk increases with duration of use. Some data suggests there is a slightly lower risk with cyclical rather than continuous regimens35. Both estrogen-only and combined HRT are associated with an increased risk of stroke and VTE, and combined HRT is linked to an increased risk of coronary heart disease, dependent on the patient’s cardiovascular risk factors, age and duration of HRT3, 35. Transdermal estrogen appears not to increase the risk of VTE and is the preferred option for women with risk factors for VTE or cardiovascular disease36. Compared to systemic HRT, intravaginal estrogen is not associated with an increased risk of cardiovascular disease, VTE or breast cancer development and long term use is generally considered safe3.

Adverse Effects of HRT 

The majority of adverse effects experienced by women using HRT are related to the effects of estrogen in the body. Some local skin irritation or contact dermatitis can occur with topical formulations (i.e., patches and gel). Common adverse reactions can include breast enlargement or tenderness, headache, irregular or breakthrough bleeding, mood changes and nausea35. Pharmacists should counsel patients that tolerance to adverse effects may develop during the first few months of therapy. However, if adverse effects are persistent or intolerable, patients should be referred to their GP to consider reducing the dose, changing to an alternative estrogen/progestogen, or changing the route of administration. 

Counselling Points for HRT 

  • Patches: should be applied to clean, dry skin on the lower abdomen or buttocks; rotate the site of application when changing patches; dispose of used patches safely 

  • Gel: rub contents onto lower abdominal region or thighs (Sandrena) or apply gel to large area of clean, dry skin on arms/shoulders/inner thighs (Estrogel) 

  • Oral tablets: taking with food can help reduce the likelihood of nausea

Table 1. Types of Systemic Hormonal Replacement Therapy (HRT) and Appropriate Subgroups of Menopausal Patients

Table 2. Systemic HRT Preparations available in Australia (table adapted from Therapeutic Guidelines)3

View Table 2

Non-Hormonal Drug Therapy 

A variety of non-hormonal pharmacological options are used ‘off-label’ to treat the vasomotor symptoms of menopause; however, evidence for their efficacy is controversial and limited to short-term studies. Choice of non-hormonal agents should be based on individualised assessment of patterns of vasomotor symptoms, comorbidities, concurrent medications, adverse effect profiles and patient preference3. For all non-hormonal therapies, dosing should start low and be titrated to patient response. Pharmacists should educate patients regarding their onset of action, which is usually evident within 4 weeks at an effective dose, but their full effect may take up to 8 weeks3.

Antidepressants

Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and noradrenaline reuptake inhibitors (SNRIs) have shown evidence of mild to moderate efficacy in reducing hot flushes and mood symptoms38, 39. They are also associated with improving quality of life and sleep3.

Gabapentin

Gabapentin can be considered as an alternative for patients who have contraindications to hormonal therapies and literature suggests it reduces the frequency and severity of vasomotor symptoms at a comparable rate to SSRIs/SNRIs39. Current guidelines suggest its suitability if hot flushes are worse at night or accompanied by poor sleep or neuropathic pain3, 39.

Clonidine

Clonidine is a centrally acting α2-agonist that has historically been a popular choice for the treatment of vasomotor symptoms. However, literature suggests modest efficacy compared to placebo, and its associated adverse effects such as dizziness, hypotension and dry mouth limits its place in current therapy35, 38, 39. 

Compounded and Complementary Therapies 

Compounded and complementary therapies are generally not recommended due to limited and conflicting evidence of safety and efficacy. Compounded ‘bio-identical’ hormone therapy, which contains a variety of estrogens, progestogens and other hormones are not subject to the same regulations as TGA-approved pharmaceutical products and the strength and purity of ingredients in these preparations can be inconsistent and there has been evidence of harms associated with their use3. 

Placebo-controlled clinical studies of complementary and alternative medicines (CAMs) to treat menopausal hot flushes found inconsistent evidence of efficacy for the use of1, 3, 38, 40, 41:

  • Vitamin E supplements – generally safe to use, although may increase bleeding risk when used with warfarin or other anticoagulants 

  • Phytoestrogen supplements (isoflavones and red clover) – safety in breast cancer has not yet been established

  • Black cohosh – serious cases of liver toxicity have been reported with its use

  • Evening primrose oil – generally safe to use, although there have been some reports of immunosuppression and thrombosis

  • Multivitamins or minerals including magnesium supplements, selenium, vitamin C – evidence of benefit is extremely limited 

  • Other herbal/botanicals including dong quai, ginseng, gingko biloba, valerian roots – evidence of benefit is extremely limited 

Non-Pharmacological Treatments 

Non-pharmacological therapies for the management of menopausal symptoms have not been as extensively explored, and evidence of efficacy is controversial and limited. 

Lifestyle Modifications 

  • Weight loss – shown to reduce vasomotor symptoms in overweight and obese individuals1, 3

  • Improving cooling through environmental control – adjusting clothing, using fans or air-conditioning as required, cold packs and drinking iced water may help lower core body temperature1

  • Avoiding triggers of vasomotor symptoms – potential triggers may include consumption of spicy foods, smoking and drinking alcohol1

  • Regular exercise – although existing evidence does not show exercise reduces vasomotor symptoms, it is associated with other benefits such as improving quality of life, cognitive function and mood, bone density, weight maintenance and cardiovascular disease1, 3

Mind/Body-Based Therapies and Practices 

  • Cognitive behavioural therapy (CBT) – evidence suggests it reduces vasomotor symptoms and improves mood, quality of life, sleep, sexual function, and general wellbeing. This approach could be used in conjunction with other therapies for menopausal symptoms3, 39

  • Hypnosis – some evidence demonstrates reduction in vasomotor symptoms (hot flushes) and improved sleep quality42 

  • Acupuncture, chiropractic intervention, paced breathing, relaxation therapy, yoga, magnetic therapy, reflexology – no evidence of any overall benefit to support recommendation of these alternative therapies1, 3

Conclusion

In summary, the management of menopause is a multifaceted and complex process, and pharmacists play a pivotal role in providing valuable support and guidance to women navigating this transitional phase of life. Menopause can trigger a wide variety of different physical symptoms and emotional challenges, and pharmacists are well-equipped to offer informed advice on the risks and benefits of treatment options and lifestyle modifications. By serving as accessible and trusted healthcare professionals, pharmacists can ensure individuals make choices that align with their unique needs and preferences. By fostering ongoing relationships with patients, pharmacists can monitor patient response to therapy and support patients with management of adverse effects, recommending referral and communication with GPs as required. Through this collaborative approach, pharmacists can assist in enhancing the effectiveness of menopausal management strategies, helping women confidently achieve quality of life and symptom control during this transitional phase of their life. 

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