Hormone Replacement Therapy (HRT) can be given as an oral medication of oestrogen with or without progesterone, as an oestrogen-impregnated patch, as a vaginal cream or pessary, or as an oestrogen (and sometimes testosterone) implant.
Oestrogen combined with a progestogen is the form of hormone replacement therapy recommended for women who have not had a hysterectomy. The preparations might be in the form of separate or combination tablets, or patches that have non-varying levels of oestrogen and progestogen. This is referred to as ‘continuous’ Hormone Replacement Therapy. Alternatively, ‘sequential’ hormone replacement therapy contains oestrogen only in tablets or patches for about fourteen days and then oestrogen with progestogen for another ten to fourteen days. With sequential hormone replacement therapy (HRT), larger-dose progestogens are used to transform the endometrium so that it will shed when the drug is withdrawn. With continuous hormone replacement therapy (HRT), smaller doses are used and the endometrium tends to atrophy and is thought to be less prone to cancerous change.
Sequential Hormone Replacement Therapy
Sequential hormone replacement therapy consists of continuous oestrogens prescribed with intermittent progestogens and is usually given to peri-menopausal women short term to treat menopausal symptoms. A withdrawal bleed will usually occur when the progestogen portion of the treatment is stopped. This form of hormone replacement therapy is better tolerated by peri-menopausal women who still have endogenous hormone production which can override the effects of the replacement hormones and cause erratic uterine bleeding. Sequential hormone replacement therapy can be prescribed in the form of tablets or patches.
Some tablets are packaged like the Pill in blister packs and one tablet is taken daily. The first fourteen tablets contain oestrogen alone and the next contain oestrogen and a progestogen, usually norethisterone acetate, medroxyprogesterone acetate or dydrogesterone. Brands include Divina, Femoston, Premia 5 and 10, Trisequens and Trisequens Forte. Climen and Climen 28 contain cyproterone acetate and are useful for those women who develop hirsutism secondary to low oestrogen and a relative over-exposure to the effects of androgens during the menopause. Other tablet forms of sequential hormone replacement therapy are Menoprem and Provelle-14, which are conjugated oestrogens given continuously with a separate tablet of medroxyprogesterone acetate from days 15-28 of the cycle.
The sequential patches Estracombi and Estalis Sequi consist of oestrogen for two weeks, then a combined patch of oestrogen with a progestogen for two weeks. They are changed every three to four days. Estrapak-50 is an oestradiol-containing patch that is combined with oral medroxyprogesterone acetate 10 mg for ten-fourteen days of the 2 8-day cycle.
It is not clear whether sequential hormone replacement therapy carries similar risks to that shown with the same type of continuous Hormone Replacement Therapy. It has been proposed that fewer days of progestogens may reduce risk of cardiovascular disease and be safer for long-term use for those women with osteoporosis. This is a less popular method of hormone replacement therapy for older women who do not usually want to be troubled by menstrual bleeding years after it would normally have stopped.
Continuous Hormone Replacement Therapy
Post-menopausal women are usually prescribed continuous hormone replacement therapy as either tablets or patches. The smaller doses of progestogen ensure endometrial thinning which reduces the risk of hyperplastic change and uterine bleeding. The main indications for this type of hormone replacement therapy are menopausal symptoms or osteoporosis.
Conjugated equine oestrogens and medroxyprogesterone acetate were the type of continuous hormone replacement therapy involved in the WHI trial of postmenopausal women. WHI revealed that healthy women should not use this type of hormone replacement therapy regime for prevention of disease because they were more likely to develop an illness than prevent one. The trial was stopped after 5.2 years instead of the planned 8.5 years because of these findings.
For post-menopausal women with osteoporosis, continuous hormone replacement therapy is still considered a valuable treatment, especially when used for no more than five years and by women with low risk factors for cardiovascular disease or breast cancer. When there is evidence of substantial risk of these diseases, other drug options should be considered. For those women with osteoporosis who are considering going off hormone replacement therapy or who have already done so, carefully considered advice should be given regarding the options available to them to manage this condition. The non-drug options are limited, and at this stage cannot be backed by clinical trials. These issues are discussed in more detail in the section on osteoporosis.
Continuous hormone replacement therapy is available as low-dose daily progestogens combined with oestrogens in one tablet:
• Premia 2.5 Continuous: conjugated equine oestrogens 0.625 mg with medroxyprogesterone 2.5 mg, one tablet daily. Premia 5 continuous contains 5 mg medroxyprogesterone acetate.
• Kliovance: oestradiol 1 mg, norethisterone 0.5 mg, one tablet daily.
• Kliogest: oestradiol 2 mg, norethisterone 1 mg, one tablet daily.
Continuous oestrogen plus progestogen can also be given as two separate tablets:
• Menoprem Continuous: conjugated equine oestrogens 0.625 mg with medroxyprogesterone 5 mg, one tablet of each daily.
• Provelle 28: conjugated equine oestrogens 0.625 mg with medroxyprogesterone 5 mg, one tablet of each daily.
The combined oestrogen and progestogen patch is Estalis. Two strengths are available each containing oestradiol 50 meg with either norethisterone 140 meg or 250 meg per patch, one patch every three to four days.