Dec 1, 2002

This page, as well as several other hormone-oriented ones on this site, is to some extent outdated, attitudes to Menopausal Hormone Therapy (in itself a significant change of name - note the abandonment of the term "Replacement") having undergone a major shift over the last few months. However, the page remains here as a record of earlier attitudes, as well as evidence against repeated claims that the WHI (E and P arm) results were a  "bombshell" and "unexpected." For more detail see the WHI page

By now, most major medical organizations have reviewed their recommendations about combination menopausal hormonal therapy and there is little to differentiate them. In general they say:

While treatment for hot flashes and other perimenopausal symptoms remains an option, a woman should be carefully counselled about the risks involved and an individual assessment made of her personal situation. Caution should be exercised about prolonged use.

Routine use of such therapy for the prevention of chronic postmenopausal conditions is not recommended;

Its use for both primary and secondary prevention of cardivascular diseas is contraindicated i.e. it should definitely not be used either both or after the development of such conditions.

Its use only for the prevention of osteoporosis should be carefully weighed against its risks, and alternative therapies such as bisphosphonates considered.

 

Until (if ever) there is evidence to the contrary, the assumption must be made that other formulations and dosages of estrogen and progestin carry the same risks as the specific ones in the study.

There is insufficient evidence as yet to decide for or against the use of unopposed estrogen as a preventive measure.

There is insufficient evidence as to whether or not phytoestrogens are protective against osteoporosis or cardiovascular disease. Many of them also list the  various herbs and supplements which are used for perimenopausal symptoms, while failing to point out that there is little or no evidence that they 'work'.

Types of OHT 

You are likely here because after weighing the risks against the hoped for benefits - maybe with the help of the "Deciding on it" link above - you have made the decision to use hormone drugs and the next thing to consider is which sort to ask for. Alternatively, maybe your doctor has "put you on" something but wasn't very informative about this something and you want to know more about it.

The first thing is, do you have a uterus? If you don't, then your task is simpler (and likelihood of benefit greater) because you will not need to balance the carcinogenic effects of estrogen on the uterine lining with a progestin.

Your choice then is between conjugated estrogens (from plant or animal - pregnant mare's urine - sources) or formulations of a single estrogen -usually estradiol, sometimes estrone and (rarely in North America) estriol. It is also possible to have specially compounded recipes made up with varying proportions of varying combinations of some or all of the three. There are also synthetic versions such as ethinyl estradiol which are more common in Europe.

You also have a choice of how the drug will gain access to your body - by mouth (pill), through the skin (patch, gel) or the vagina (cream, ring)

If however you do have a uterus then your choice is more complex. As well as making a choice of the type of estrogen, you have to choose a way of protecting that uterus. You may choose to

• Use a very low dose of estrogen - a tactic which is unproven both in terms of protection and benefit
• Submit to an endometrial biopsy at least every year and risk that any overgrowth found by it will be "cured" by progestin treatment. If it isn't, the result may be a hysterectomy. There is even a very faint chance that cancer may already be present in which case the result will be a hysterectomy
• Add a progestin.

The major divide in type of progestagen is between "natural" and the others. In this case, "natural" means that the molecular form is identical to that produced by the body naturally. The others, while very similar do have subtle differences from it. These differences may well be the reason for the greater amount of difficulty experienced by women taking them - but they may also be the reason for the protective effects which have been demonstrated over the years. We just don't know.

The "other" progestins may be divided into two main types - those derived from progesterone and those derived from testosterone.

The progesterone derivatives are more popular in North America, the best known one being medroxyprogestrone acetate (MPA) popularly referred to as Provera, though this is just one brand name among several. This is the progestin that was used in the majority of studies from which we derive much of our expectation of how the body will react to "progestins" as a class. 

Testosterone derivatives such as norethindrone acetate are more often used in Europe, though they are appearing more in N.America as European-developed types of HRT cross the Atlantic. There have been studies comparing the effects of "European style" HRT with "US style" HRT which show that the two have similar effects but to differing degrees so there is now even more need for caution when evaluating the relevance of a particular study or claim to one's own situation.
 

HRT (i.e.estrogen+progestin) may be cyclical (monthly, quarterly) or continuous (combined in a single pill or patch, or separate)

Until recently, it was customary for a woman to take estrogen every day for three or four weeks out of four but only add a progestin for 10 to 12 days a month. Once the progestin was stopped a "period" followed within a day or two. This is known as the cyclical method as it is intended to mimic the premenopausal cycle. Most studies indicate that 10 days is the minimum period of progestin use to adequately protect the uterus, and 12 is better.

Many women feel well while on estrogen only, but suffer severe side effects from the progestin. To mitigate this, there is an increasing tendency to prescribe a quarterly "bleed" so that the progestin use is limited to 10 days in 3 months. Nothing is known about the long term safety of this scenario since it hasn't been in use long term.

Many women don't want to bleed at all and in order to encourage such women to use their product, the drug companies have been trying to develop a method to achieve this while still protecting the uterus. The chief attempt is through the continuous administration of both estrogen and progestin, the dosage of progestin being reduced to compensate for the longer period of administration. The success of this method is variable from woman to woman, with episodes of unscheduled bleeding being common especially in the first year. Again there is no long term safety record and I personally see it as particularly problematic since it produces a totally unnatural state of stable levels of progesterone throughout the month rather than the customary cyclical ebbing and flowing.

( Note that whenever bleeding does not conform to the expected pattern for the specific type of drug, 
then evaluation of the cause may be necessary.)

The latest types of HRT to be introduced utilize the same synthetic hormonal compounds used in oral contraceptive pills, but in smaller doses and with varying schedules including progestin three days on then three days off. Anecdotal reports on the internet tend to give this particular one a poor report.

Note that "low dose" oral contraceptives are increasingly being prescribed to perimenopausal women despite the fact that it was originally thought that their use over the age of 35 was risky. Even though the 'low dose" pills have lower doses than the original contraceptives, they still have more drug content than HRT and are typically formulated from the more potent synthetic estrogens.  Be sure you investigate their risks thoroughly, especially if you smoke. The "third generation" pills carry greater risk of blood clotting than do the second generation ones.

Important: Before taking any drug, read the patient information sheet which should have been supplied with it.

If you want specific information about a brand name drug, the best thing to do is to consult http://rxlist.com and search on the brand name. 

You may get the choice of two links - if you are accessing the (recommended) more comprehensive information linked from the left side of the page, do not overlook the linked blue "tabs" at the top of the screen. 

You may find yourself on a generic page but the information will apply equally to the brand name version.

Information specific to the UK can be accessed through the British National Formulary which requires free registration. Once registered, you can find info about oestrogens in section 6.4.1.1 and about progestogens at 6.4.1.2 

Information on oestrogens specific to Australia can be found with some difficulty through http://healthanswers.telstra.com/drugdata/search.asp?SearchLetter=1search_string=O Just look at all entires beginning with oestr. For progestagens, you will have to have the brand name and search from the base page at http://healthanswers.telstra.com/drugdata/

For New Zealand consumer information go to  http://www.medsafe.govt.nz/Consumers/cmi/CMIForm.asp and search on the relevant name

estradiol (Climara, Vivelle, Estraderm, Estrace, Estring, Vagifem) then go to http://www.rxlist.com/cgi/generic/estrad.htm and/or http://www.rxlist.com/cgi/generic2/estradtd.htm (transdermal)

conjugated horse estrogens (Premarin) then go to  http://www.rxlist.com/cgi/generic/conest.htm

conjugated plant estrogens (Cenestin, C.E.E) http://www.rxlist.com/cgi/generic/cenestin.htm

esterified estrogens (Estratab, Menest): http://www.rxlist.com/frame/display.cgi?drug=ESTRATAB

ethinyl estradiol http://www.rxlist.com/cgi/generic3/estinyl_ids.htm

norethindrone acetate (Aygestin):  http://www.rxlist.com/cgi/generic/norestoc.htm  which refers to contraceptive use but it is the same drug.

medroxyprogesterone acetate (Provera, Cycrin) : http://www.rxlist.com/cgi/generic/medrox.htm

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