Cyclical combined systemic MHT
Cyclical combined menopausal hormone therapy (MHT) uses progestogen for only a portion of each cycle (10 to 14 days), which induces a monthly withdrawal bleed. It uses a higher dose of progestogen than that used in continuous regimens.
Observational data suggest that long-term use of cyclical combined MHT is associated with an increased risk of endometrial cancer compared to continuous combined MHT1. Review cyclical MHT after 5 years and consider switching to continuous combined MHT; for those who wish to continue cyclical combined MHT, refer to a specialist for discussion.
Indications for cyclical combined MHT are listed in Types of systemic menopausal hormone therapy and the appropriate subgroups of menopausal patients. Before starting systemic MHT, individualised assessment of the expected benefits and harms of treatment is needed. For a suggested approach to starting menopausal therapy, including considerations in choosing between oral and transdermal estrogen, see Approach to starting therapy for menopause.
Combined MHT regimens can be achieved using a single formulation containing estrogen plus progestogen, or separate estrogen and progestogen preparations. Use of separate formulations simplifies dose titration, but combined formulations are easier to use and improve adherence. Consider patient preference for formulation.
For cyclical combined MHT, use:
If a suitable combination product is not available, or if separate estrogen and progestogen formulations are preferred, use:
estrogen in a low dose, orally or transdermally (see c_srg2-c24-s7.html#srg2-c24-s7__tsrg2-c24-tbl3 for dosage and formulations); increase dose if needed (depending on symptoms, age and comorbidities) menopause, combination therapy (cyclical)
PLUS ONE OF THE FOLLOWING
1 norethisterone 2.5 to 5 mg orally, daily for the same 10 to 14 days of each calendar month2 menopause, combination therapy (cyclical) norethisterone
OR
1 progesterone (micronised) 200 mg orally, daily at night for the same 12 to 14 days of each calendar month23 menopause, combination therapy (cyclical) progesterone (micronised)
OR
2 medroxyprogesterone 10 mg orally, daily for the same 10 to 14 days of each calendar month2. menopause, combination therapy (cyclical) medroxyprogesterone
See Monitoring systemic MHT and Managing adverse effects of systemic MHT for guidance on adjusting cyclical combined MHT.
Transdermal estradiol with cyclical micronised progesterone best approximates physiological hormones (‘body-identical’ MHT). This combination may have fewer harms (eg risk of venous thromboembolism) than other combined MHT formulations. Body-identical MHT is not to be confused with compounded bio-identical hormone therapy, which should not be used.
If avoidance of withdrawal bleeds is desired and it has been 1 year or longer since the final menstrual period, change from a cyclical progestogen to continuous combined MHT or offer conjugated estrogens+bazedoxifene or tibolone.
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low-dose estrogen with cyclical progestogen medium-dose estrogen with cyclical progestogen | ||
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Estrogen (continuous) |
Progestogen (cyclical) |
Brand name examples |
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low-dose estrogen with cyclical progestogen | ||
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oral low-dose estrogen+progestogen | ||
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estradiol 1 mg (days 1 to 28) |
dydrogesterone 10 mg (days 15 to 28) |
Femoston 1/10 |
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transdermal low-dose estrogen gel and oral progestogen | ||
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estradiol 0.75 mg (1 pump of 0.06% gel) (days 1 to 28) |
micronised progesterone 200 mg for 12 to 14 consecutive days |
Estrogel Pro [NB3] |
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medium-dose estrogen with cyclical progestogen | ||
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oral medium-dose estrogen+progestogen | ||
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estradiol 2 mg (days 1 to 28) |
dydrogesterone 10 mg (days 15 to 28) |
Femoston 2/10 |
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estradiol 2 mg (days 1 to 22) estradiol 1 mg (days 23 to 28) |
norethisterone 1 mg (days 13 to 22) |
Trisequens [NB3] |
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transdermal medium-dose estrogen+progestogen patch | ||
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estradiol 50 micrograms/24 hours (days 1 to 28) |
norethisterone 140 micrograms/24 hours (days 15 to 28) |
Estalis Sequi 50/140 (apply twice weekly) |
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estradiol 50 micrograms/24 hours (days 1 to 28) |
norethisterone 250 micrograms/24 hours (days 15 to 28) |
Estalis Sequi 50/250 (apply twice weekly) |
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transdermal medium-dose estrogen gel and oral progestogen | ||
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estradiol 1.5 mg (2 pumps of 0.06% gel) (days 1 to 28) |
micronised progesterone 200 mg for 12 to 14 consecutive days |
Estrogel Pro [NB3] |
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Note:
NB1: A progestogen is required to prevent endometrial hyperplasia in individuals with a uterus, including those who have had endometrial ablation or subtotal hysterectomy. Some individuals with significant endometriosis may require a progestogen to prevent stimulation of endometrial deposits and malignant transformation (even if they have had a total hysterectomy); seek specialist advice. NB2: This list may not be complete. NB3: Not available on the Pharmaceutical Benefits Scheme (PBS) at the time of writing. See the PBS website for current information. NB4: Micronised progesterone should be taken at night because it can cause drowsiness; this can be beneficial in individuals with sleep disturbance. | ||