Women who have had a hysterectomy can use oestrogen replacement without taking progestogens for endometrial protection. A woman who has an intact uterus will need to take progestogens either continuously at a small dose to cause endometrial atrophy, or cyclically at a higher dose, to simulate the protective effect of cyclic endometrial shedding.
The types of oestrogens available are the natural oestrogens (oestradiol, oestriol or oestrone), synthetic oestrogens (dienoestrol, ethynyloestradiol), and conjugated equine oestrogens (Premarin). The natural oestrogens are favoured over the synthetic versions because they cause fewer liver-related side-effects, they are metabolised quickly, exert weaker oestrogenic effects, and are less likely to cause problems with long-term use.
Oestrogen in tablet form is recommended for menopausal symptoms such as hot flushes and may be suggested to prevent or treat osteoporosis.
• Premarin: a conjugated form of oestrogen synthesised from pregnant mares’ urine.
Dose range: 0.3-1.25 mg daily.
• Progynova: oestradiol valerate. This oestrogen is fairly rapidly metabolised and excreted, with less adverse affect on the liver than some other forms of oestrogen.
Dose range: 1.0 mg-4.0 mg daily.
• Estrofem: micronised oestradiol. This is one of the natural oestrogens and is available as 1 mg, 2 mg and 4 mg tablets.
Dose range: 1 mg-4 mg.
• Zumenon: micronised oestradiol. Available only as a 2 mg tablet. Dose: 2 mg daily.
• Genoral and Ogen: piperazine oestrone sulphate. Dose range: 0.625 mg-2.5 mg.
• Ovestin: oestriol. Needs to be given in large doses, but has very little effect on the endometrium and its use is associated with minimal vaginal bleeding.
Dose range: 1.00 mg-4.00 mg.
Patches and gels
Patches take advantage of the fact that oestrogen absorption through the skin is very efficient. An oestrogen-impregnated, adhesive patch is applied to the skin, usually the buttock, through which oestrogen is easily absorbed into the body. Climara, Dermestril, Estraderm, Femtran and Menorest are the names of commonly available patches. Gels containing oestrogen, such as Sandrena, are also available and are rubbed onto the skin daily. The benefits and risks of oestrogen patches and gels as compared to oestrogen tablets are not yet established, but patches are much less likely to cause nausea or liver and gall bladder problems because transdermal applications of oestrogen avoid the first pass effect (via the liver) of oral oestrogens. The dose of oestrogen in patches and gels is therefore lower because of the lower initial rate of hepatic conjugation and excretion.
Oestrogen patches are usually prescribed for menopausal women, but other conditions can also respond to oestrogen replacement therapy. Transdermal oestradiol has been tested in women with premenstrual syndrome as a method of blocking ovulation and creating a hormonal picture similar to the asymptomatic follicular phase of the cycle. A progestogen is also necessary as part of the therapeutic regimen to prevent uterine endometrial hyperplasia. Patches delivering 100 meg of oestradiol per day (plus ten days of progestogen) bring symptom relief and block ovulation. Oestrogen patches are also sometimes effective for women who experience menstrual migraines. They are applied during the late luteal and early follicular phase of the cycle.
Patches are changed once or twice weekly, depending on the formulation, and must be applied to a different area each time. They cause skin irritation in between 10-20 per cent of women, which is reduced if the alcohol in the patch is allowed to evaporate prior to application. Oestrogen absorption through patches is accelerated when body temperature rises and sweating occurs. It is advisable that the patch be removed during strenuous exercise or other activities that increase the skin temperature.
• Climara: 2 mg, 3.8 mg, 5.7 mg and 7.6 mg patches containing oestradiol that release 25, 50, 75 and 100 meg per 24 hours respectively. The patches are changed weekly.
• Dermestril: oestradiol patches in strengths of 2 mg, 4 mg and 8 mg that are changed every 3-4 days.
• Estraderm: oestradiol patch of different strengths (2 mg, 4 mg and 8 mg), which release 25 meg, 50 meg and 100 meg respectively. The 4 mg patch that releases 50 meg is equivalent to 0.625 mg of Premarin and is favoured as the protective dose for prevention of osteoporosis.
• Femtran: oestradiol patch of the same strengths as Climara and also changed weekly.
• Menorest: oestradiol patches in strengths of 3.28 mg, 4.33 mg, 6.57 mg and 8.66 mg, changed every 3-4 days.
• Sandrena gel: a gel containing oestradiol at a dose of 1 mg per sachet. The gel is applied daily.
Vaginal creams, pessaries or rings
Oestrogen can be inserted as a vaginal cream, pessary or ring for the treatment of atrophic vaginitis or other urogenital symptoms such as urinary frequency or stress incontinence. Vaginal creams are inserted with a dose-determined applicator and typical treatment regimes are described below.
• Ovestin contains oestriol at a dose of 1 mg/g. The cream is inserted every night for three weeks and then twice weekly.
• Premarin contains conjugated equine oestrogens at 0.0625 per cent. Premarin cream is used at doses of 0.5-2 g daily for three weeks with one week off.
It is recommended that women see the prescribing doctor about three months after commencing these treatments.
Pessaries available are Ovestin Ovula (oestriol) or Vagifem (oestradiol) and are similarly indicated for atrophic vaginitis. Both are used every night for two to three weeks then twice weekly after that, with a reassessment in three months. Oestrogen-impregnated rings are used less often but are indicated for symptoms associated with oestrogen deficiency in the genitourinary system. The only ring available is ESTring. Rings must be fitted by a doctor or gynaecologist and can sometimes cause vaginal bleeding, irritation or discharge.
Creams, pessaries and rings are preferable to tablets or patches when symptoms of vaginal dryness and urinary symptoms such as burning and irritation are the only menopausal symptoms requiring treatment. Creams and pessaries have a mainly local effect on the tissues of and around the vagina and vulva and their use is associated with very low risk of heart disease or breast cancer. Creams and pessaries do not improve bone density.
Implants are small ‘tablets’ of oestrogen which are injected subcutane-ously with a local anaesthetic, usually in the lower abdomen. The oestrogen is gradually absorbed and the implant needs replacing every four to eight months or when plasma levels of oestrogen drops. Women with a uterus require a progestogen as well. Serum oestradiol levels should always be checked prior to inserting another implant because some women have been found to develop menopausal symptoms even when oestradiol levels remain high. This has meant that implants are less frequently used now. The implants are usually oestrogen alone, but sometimes oestrogen and testosterone is used, especially for women with low libido. Oestradiol implants are available in strengths of 50 mg or 100 mg.