Prescribing Issues

The best management option for the individual will vary with what is bothering her most. You will need to consider her symptom profile, her risk profile and her preferences and concerns. You will need to understand where she is in the menopause transition.

When you get to prescribing, ask yourself some simple questions, as follows.

  1. Are her symptoms general or exclusively urogenital? True menopausal symptoms derive from estrogen deficiency. If the flushes are tolerable but urogenital symptoms are significant, then low dose vaginal estrogens should not only be sufficient but will often be more effective as an initial strategy.
  2. Has she got a uterus? More strictly, is there possibly any endometrium remaining? If so, then as well as estrogen she will need progestogen to provide opposition and prevent hypertrophy and malignant change, as otherwise risk doubles over 5 years. If she has a levonorgestrel intrauterine system (LNG IUS) which has been in place over five years but is deemed adequate for contraception at her age, she will still need additional progestogen.
  3. Has she had a period in the last year? If so, she should be offered a cyclical regimen unless she already has an in-date Mirena ® LNG IUS. If so, only estrogen is needed. If she has not had a period in the last year, she will need either continuous progestogen and estrogen or tibolone.
  4. Does she have any significant cardiovascular risk factors, gallstones, thyroid replacement therapy or other metabolic issues, which indicate a non-oral estrogen is preferable?
  5. What does she want to use?
  6. Does she need contraception?

Figure 1 shows a menopause clinical pathway highlighting history, examination and management including hormonal treatment.

Hormonal therapy

Oral estrogen is available in three formats:

  • conjugated equine estrogen which is a complex mixture derived from the urine of pregnant mares
  • estradiol valerate
  • micronised 17β estradiol

The latter is my oral format of choice, with conjugated equine estrogen as the alternative. Women happy with any one do not need to change. 17β estradiol is the most important systemically active estrogen in vivo, and is the type of estrogen used in non-oral preparations such as patches or gel.

Patches should be changed once or twice a week dependent on brand, while gel has to be applied daily. There are pros and cons to both and the option should ultimately be the choice of the woman. Bioavailability will differ between women but as a rough approximation, 1.5mg estradiol delivered as gel = 50mcg/day from a patch = 2mg oral estradiol 17β.

Progestogens fall into different classes, and the two to familiarise yourself with are the testosterone derivatives (C19 progestogens such as levonorgestrel and norethisterone) and the progesterone derivatives (C21 – progesterone, dydrogesterone and medroxyprogesterone acetate). The activity at the testosterone receptor is one of the factors that result in different responses to different progestogens and if your patient appears intolerant, change class.

It is helpful to work out which types of estrogen and progestogen are available in the marketed products. This enables you to develop a simple formulary to allow low start and standard cyclical combinations, to move to continuous within the same family, and then progressively to drop the dose as women generally can be managed with lower doses over time.

Figure 2 shows the basis of a simple limited oral HRT formulary, although other options are available.

If your patient has previously has had no issues with a first line 30mcg ethinylestradiol/150mcg levonorgestrel combined oral contraceptive and her cardiovascular risk profile is satisfactory, then a 17β estradiol + norethisterone oral combination is likely to suit. If she has had progestogen-related side effects in the past, a C21 combination could be chosen initially.

Some patch brands offer sequential and continuous regimens with C19 progestogens. Cutaneous absorption of C21 progestogens is limited but there is the option of developing a bespoke regimen using estrogen only with either;

  • micronised oral progesterone (200mg cyclically for 12-14 days a month or 100mg daily for continuous use). This has a sedative profile so it can be helpful to take at night
  • medroxyprogesterone acetate (10mg cyclically or 5mg continuously)

The general rule is to start with a low estrogen dose (such as 1mg oral) and then increase if needed, unless your patient is under 45. Such women often have a higher replacement requirement and should be started at standard doses.

Warn her that if she is given a cyclical preparation, two prescription charges will be levied and provide three months’ supply. Review before she runs out; considering her symptoms, her reaction to the product, bleeding pattern and risk profile. Modify if necessary considering estrogen dose and route and then the progestogen.

Once stable, review annually but aim to move women to a continuous regimen by about five years, as this has been shown to give best protection. With time, dose requirement to manage symptoms does reduce and women can be reassured that the dose needed to maintain bone density is quite low so they will not lose protection.

There is no limit as to how long HRT can be prescribed. It is an individual decision, reviewed annually, with the risks and benefits discussed, such that the decision to continue is informed. In women below the typical age of menopause (51-52) replacement can be seen as protective. HRT is not delaying the inevitable, if symptoms return they would have been present anyway and the lowest effective dose is always sought.

Menopause often comes when there are other significant challenges in women’s lives. Helping your patient to cope may not just give her life back but have a cascading effect on those around her. The risks are few, the rewards can be great – do not be afraid to prescribe what she is missing.