Menopause, or climacteric, is a change that occurs and profoundly impacts the lives of half the world’s population at some point. Best practices in the clinical management of this transition have been published earlier, in 2014, as the The Practitioner’s Toolkit for Managing the Menopause. The revised Toolkit has now been released, incorporating newer published findings for optimal clinical care.
The original Toolkit was intended to present an easy-to-use framework for practitioners while evaluating and treating menopause-related conditions. It was endorsed by the International Menopause Society and is used worldwide.
The authors of the revised 2023 Toolkit extracted key recommendations from professional guidelines and positions as well as consensus statements on menopause and related conditions that have emerged since 2014.
The Toolkit, published in Climacteric, begins with definitions and a brief description of menopause-related physiology and pathophysiology. It presents menopausal symptoms that may or may not be treated with menopausal hormone therapy (MHT) and guidelines on the history to be obtained.
Based on current literature, it includes flow charts to guide the diagnosis, evaluation, and management of women suffering from clinical conditions associated with menopause.
It provides clinical algorithms to help decide if the woman is menopausal or otherwise. It also guides the choice of hormonal or non-hormonal therapy. It also incorporates newer therapies, subject to availability and regulatory restrictions that vary between countries.
The Toolkit includes a spectrum of management options that may be shared with the woman to help her make shared decisions about her care. An example is the choice to use MHT in situations without current guidelines, such as the prevention of fractures due to bone loss in asymptomatic postmenopausal women.
The Toolkit has received commendation from multiple professional bodies concerned with women’s health during menopause, including the International Menopause Society, Australasian Menopause Society, and British Menopause Society.
Menopause refers to “the permanent cessation of menstruation in a non-hysterectomized woman.” However, while this may be academically accurate, it does not cover women who are not menstruating before menopause due to, for instance, hysterectomy.
This has led to the more reasonable definition of menopause as “the permanent cessation of ovarian function.” The average age varies from 45 to 55 years in wealthy countries but is earlier in developing countries, requiring clinicians to make appropriate adjustments when diagnosing early menopause or premature ovarian insufficiency (POI) based on the Toolkit definitions.
The authors discuss the need for and relative accuracy of hormonal assays as predictors of menopause, as well as menstrual cycle-based stages of menopause as per the STRAW+10 classification by the Stages of Reproductive Ageing Workshop (STRAW).
The differential diagnoses are also to be excluded, such as thyroid disease or central causes of amenorrhea, as well as conditions like iron deficiency that are associated with non-specific symptoms like fatigue.
Symptoms during the transition may be due to a relative excess of estrogen or too little estrogen, or both. Many symptoms are not specific to menopause.
Those related to estrogen insufficiency include vasomotor symptoms (VMS), hot flushes, sweats, and symptoms related to the urinary and reproductive tract. These are used as a basis for offering MHT.
VMS are reported by three-quarters of women who have gone through menopause and continue to be present in a third of women between 65 and 80 years. These symptoms reduce wellbeing markedly, similar to housing insecurity.
Moderate to severe VMS are associated with three-fold higher odds of moderate to severe depressive symptoms compared to the absence of VMS.
Other symptoms during this period include low mood, sleep disruption, low libido, anxiety, and irritability. Musculoskeletal symptoms during this period are more common in Asian women and often respond to MHT.
In contrast, cognitive symptoms are not treated with MHT in the absence of evidence of effectiveness, and a research gap has been identified in this area.
Other changes related to the lowering of estrogen include visceral fat deposition, type 2 diabetes, cardiovascular disease, hyperlipidemia, and faster bone loss beginning before the last menstruation. The risk of fracture goes up, and some have also reported perimenopausal loss of verbal memory.
Management of menopausal symptoms
Both lifestyle and medical management measures are laid out. Lifestyle risk factors include good dietary patterns, physical exercise, avoiding smoking and excessive drinking, and stress relief. Regular monitoring for cardiovascular risk factors, including hypertension and high cholesterol, diabetes, and cancers of the breast or reproductive tract, is also recommended.
Menopausal hormone therapy is regarded, by the best Clinical Practice Guidelines (CPGs), as the most effective treatment for VMS. MHT must include a progestogen to protect the endometrium, whenever present, against cancer. The use of oral estrogen increases the risk of venous thromboembolism (VTE), especially above the age of 60 years, making the transdermal route preferable for high-risk women.
Androgens are of limited use, with only testosterone being indicated for low libido alone.
A combination of estrogen and progesterone MHT is used to control VMS, sleep disturbances, mood changes, and urogenital dryness, as well as musculoskeletal symptoms.
Combined MHT may be used cyclically, with scheduled bleeding occurring every month or continuously if an LNG-IUD is in place. The latter may cause breakthrough bleeding for a few months, but 90% are amenorrheic at one year.
Estrogen alone is used following a total hysterectomy. Possible routes include oral, transdermal, vaginal rings, or pellet implants, though the last is mostly unregulated. Estrogen pessaries and creams are suitable for managing urogenital symptoms.
Other therapies include estrogen in combination with a selective estrogen receptor modulator (SERM) instead of progesterone and testosterone (to improve libido alone). The effectiveness of MHT in VMS and sleep disruption is documented, but not for depressive symptoms. Nutritional and plant supplements are not useful for moderate to severe VMS, and neither have exercise and stress relief.
Non-hormonal interventions with some effectiveness cognitive behavioral therapy (CBT), which significantly alleviates VMS; and those of variable efficacy like selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors, low-dose oxybutynin, gabapentin, fezolinetant (a centrally acting drug), and clonidine. A highly-skilled surgical procedure called stellate ganglion blockade also relieves severe VMS for up to three months but is limited in availability.
The management of menstrual cycle disruption, contraception, and menopausal symptoms in perimenopausal women is also laid out. The combined oral contraceptive pill (COCP) helps with all three areas, but individual evaluation is essential to minimize the risks of VTE and other adverse events.
Non-oral routes of administration are available in some countries that help to control cyclical bleeding alone. Women may migrate to MHT once they no longer need COCP.
The levonorgestrel-releasing intrauterine devices (LNG-IUDs) are a progestogen-only approach that provides endometrial suppression. It minimizes bleeding in women with menorrhagia. These can be combined with estrogen and protect the endometrium for up to five years.
Other progestin-only oral contraceptives may relieve certain symptoms and provide contraception when estradiol is contraindicated. Short-course progesterone is also useful to regularize cyclical bleeding.
MHT and osteopenia
MHT could help treat women with osteopenia before the age of 65 with other risk factors for fractures. The authors also propose a bone density cut-off to recommend MHT, along with the body mass index (BMI) and time since menopause of each woman.
For postmenopausal women, MHT prevents bone fractures by arresting bone loss, regardless of other risk factors, and may be recommended for asymptomatic above-65 women unless the risk is too great.
The risks of systemic MHT include VTE (for oral estrogen-containing formulations), and breast cancer risk (for oral COCP but not estrogen alone). Progesterone carries a lower breast cancer risk than synthetic estrogens, but more evidence from randomized controlled trials is required.
Tibolone, while mostly safe in these respects, slightly increases the risk of ischemic stroke but reduces colon and breast cancer risk by ~70%.
A change of regimen often relieves the adverse effects of MHT. Follow-up is advised for systemic MHT for evaluation, dose adjustment, testing, and to discuss patient issues with the drugs.
“To our knowledge, this remains the only clinical practice tool for menopause-related care that has international application.” The authors aim to provide a basic standard of evidence-based best care practices for any woman, irrespective of geographical or other limitations. The wide range of options it covers encourages clinicians to discuss and educate women about the choices available before making a shared decision on their management.