Estrogens
| Type | Recommendation |
|---|---|
| When to deprescribe | |
| CBR |
Systemic Menopausal Hormone Therapy (MHT) We suggest deprescribing be offered to older women taking MHT (menopausal hormone therapy i.e. estrogen monotherapy or estrogen combined with progestogen) whose menopausal symptoms have resolved or improved over time, provided this aligns with the individual's goals and preferences and following informed consent. Vaginal MHT We suggest deprescribing be offered to older women on low-dose vaginal estrogen therapy for genitourinary syndrome of menopause whose symptoms have resolved or improved over time. |
| Ongoing treatment | |
| CBR |
We suggest continuing MHT in people who experience symptoms recurrence that impact their quality of life and cannot be managed with non-hormonal options. If deprescribing is unsuccessful, we suggest non-hormonal and non-pharmacological therapies (e.g. lifestyle interventions) for genitourinary syndrome of menopause such as moisturisers, lubricants or pelvic floor muscle exercises may be considered as alternative options before considering the reinitiation of MHT. If MHT needs to be resumed, we suggest maintaining the lowest effective dose; however, we suggest reassessing the need for long-term therapy periodically including the possibility of switching to another route of administration (e.g. topical low-dose estrogen intravaginal cream for localised symptoms). |
| How to deprescribe | |
| CBR |
We suggest stopping MHT abruptly without the need for tapering; however, some patients may prefer gradual tapering by reducing the dose or dosing frequency. For oral formulations, we suggest reducing one dose per week every two to four weeks (e.g. reducing from daily administration to six days a week with one day off for two to four weeks, then to five days a week for two to four weeks, and so on, until discontinuation). For transdermal formulations, we suggest gradually reducing the strength of the patch over three to six months, depending on the available preparations. For gel, cream or pessary formulations, we suggest tapering by reducing the dosing frequency every two to four weeks. |
| Monitoring | |
| CBR |
We suggest periodic evaluation of patient preferences, symptom control and ongoing benefit-risk profile including fracture risk (e.g. using Fracture Risk Assessment Tool) and if indicated, bone mineral density, as well as consideration for alternative treatments for management of osteoporosis if required. |
CBR, consensus-based recommendation
Estrogens are widely used as menopausal hormone therapy (MHT) to alleviate menopausal symptoms and prevent bone loss resulting from decreased endogenous estradiol production [177]. However, the decision to use MHT must be carefully balanced against the potential risks, including an increased risk of cardiovascular disease and estrogen-dependent cancers, such as breast cancer, with the risk increasing with prolonged use [177]. The Australasian Menopause Society provides information for healthcare professionals about non-hormonal treatments for menopausal symptoms, along with guidance on other aspects of women's health through midlife health and menopause [418].
Genitourinary Syndrome of Menopause (GSM) refers to atrophic symptoms in the vulvovaginal and bladder-urethral regions resulting from the menopause-related loss of estrogen [419]. GSM affects an estimated 40% to 90% of postmenopausal women and can significantly impact their quality of life [420]. First-line treatment for GSM typically includes non-hormonal moisturisers, lubricants, and pelvic floor muscle exercises. If these measures do not provide sufficient symptom relief, vaginal estrogen therapy or other hormonal treatments may be considered [419]. For moderate-to-severe vaginal atrophy unresponsive to non-hormonal therapy, low-dose vaginal estrogen may be considered if there is no absolute contraindication. In Australia, commonly used formulations include estriol 1 mg/g cream, estriol 500 mcg pessary, and estradiol 10 mcg pessary. Estradiol has a greater effect on systemic estrogen levels and is therefore considered a second-line option [421].
Refer to the narrative evidence summary, the GRADE Summary of Findings table in the guidelines, and the Technical Report for a complete presentation of the deprescribing evidence based on the GRADE framework (including other factors considered in developing the recommendations).
Vaginal MHT
The standard dosing regimen involves daily application for the first two weeks, followed by maintenance therapy once or twice weekly. Low-dose vaginal estrogen can also be used alongside systemic MHT if atrophic symptoms persist. Long-term use of vaginal MHT is generally considered safe due to minimal systemic absorption; however, evidence from trials beyond one year is limited [422]. The need for continued therapy should be reassessed based on symptom progression and individual preferences. If symptoms have resolved or improved, a trial discontinuation may be appropriate, with the option to restart therapy if needed.
Systemic MHT
The greatest benefits of systemic MHT are observed in women within 10 years of menopause onset and those under 60 years of age [422]. As a result, MHT is generally recommended for a maximum duration of five years and is typically avoided in individuals over the age of 60. However, treatment should be individualised, with dosing adjusted based on symptom response rather than age alone. In some women over 65, continued MHT may be appropriate if the benefits, such as improved quality of life and bone loss prevention, outweigh the risks.
For those with bothersome vasomotor symptoms (e.g. hot flushes and night sweats), non-hormonal and non-pharmacological therapies should be first considered prior to commencing or reinitiating hormonal therapy. If these approaches are ineffective, hormonal use may be considered at the lowest effective dose provided the benefits and risks are carefully considered in perspective for each woman following shared decision-making [421, 422].
We identified one study related to estrogen deprescribing from the systematic review and meta-analysis [423]. This study was a comparison of the effect of deprescribing estrogen and placebo on surrogate outcomes indicative of fracture risks. There is no direct evidence of the benefits or harms related to estrogen deprescribing. The current evidence is of very low certainty and inadequate to inform evidence-based recommendations.
Key study characteristics and results
Gallagher 2002 conducted a five-year 2x2 factorial RCT comparing MHT, calcitriol, MHT with calcitriol, and placebo for three years and the effect of discontinuing therapy for two more years. All participants were women aged over 65 who did not have primary hyperparathyroidism and were not taking bisphosphonates, anticonvulsants, estrogen, fluoride, or thiazide diuretics, in the past six months. After discontinuing therapy at the end of year three, much of the bone density gained during treatment was lost in all three treatment groups, although all treated groups still had a significantly higher total body bone mineral density (BMD) compared to placebo. Compared to the group who were untreated (placebo group), the percentage change in total body BMD from baseline to five years for those who received MHT for the preceding three years before discontinuation was lower (MD 2.89, 95% CI 2.71 to 3.07) as was spinal BMD (MD 2.39, 95% CI 2.02 to 2.76), femoral neck (MD 1.33, 95% CI 0.94 to 1.72), and total hip (MD 1.19, 95% CI 0.84 to 1.54). There was no significant difference between the two groups in BMD of the trochanter (MD -0.11, 95% CI -0.55 to 0.33).
The method of deprescribing was not described in the study.
There is limited evidence on the safest method for discontinuing MHT. Guidelines suggest up to 50% of women experience symptom recurrence within four to six weeks of discontinuing systemic MHT [421]. An RCT of 81 postmenopausal women on combined estrogen-progestogen therapy compared tapering versus abrupt discontinuation. However, this study was excluded from our systematic review and meta-analysis, as the mean age at inclusion was 58 in the taper-down group and 59 in the abrupt discontinuation group (both under 65). The trial found no significant differences between the two groups in the incidence or severity of hot flashes, quality of life, or the rate of therapy reinitiation [424].
If gradual tapering is preferred, it may be implemented by reducing the dose or dosing frequency [425]. For example:
- For oral formulations, reduce one dose per week every two to four weeks; or
- For transdermal formulations, gradually lower the patch strength over a period of three to six months, depending on the available dosage forms; or
- For gel, cream or pessary formulations, reduce the dosing frequency every two to four weeks.