NEWS: 2007 guidelines from the International Menopause Society

This was exciting news at the time these came out, and since the recommendations have changed very little since then, we can hold onto them as providing a fairly durable understanding of best practices from the medical standpoint.

The document is the International Menopause Society (2007) revised "treatment" recommendations for menopause (free, pdf). 

In the post-WHI terror years, this major medical practice group promulgated some of the most restrictive and negative of the major sets of guidelines, providing frightened physicians the backup they needed to withhold HRT from many desperately miserable women.

But with additional analysis of WHI data plus results accumulating from other studies, a more rational outlook prevailed that goes back to a sensible, individualized approach. We really urge you to download and read this whole document, but the guiding principles section, which we are quoting, is excellent in terms of summarizing much of what we work with and believe here:

Hormone therapy should be part of an overall strategy including lifestyle recommendations regarding diet, exercise, smoking and alcohol for maintaining the health of postmenopausal women. HT must be individualized and tailored according to symptoms and the need for prevention, as well as personal and family history, results of relevant investigations, the woman's preferences and expectations. The risks and benefits of HT differ for women around the time of menopause compared to those for older women. 

HT includes a wide range of hormonal products and routes of administration, with potentially different risks and benefits. Thus, the term `class effect' is confusing and inappropriate. 

Women experiencing a spontaneous or iatrogenic menopause before the age of 45 years and particularly before 40 are at higher risk for cardiovascular disease and osteoporosis. They will benefit from hormone replacement, which should be given at least until the normal age of menopause. 

Counselling should convey the benefits and risks of HT in simple terms, e.g. absolute numbers rather than as percentage changes from baseline expressed as a relative risk. This allows a woman and her physician to make a well-informed decision about HT. 

HT should not be recommended without a clear indication for its use. 

Women taking HT should have at least an annual consultation to include a physical examination, update of medical history, relevant laboratory and imaging investigations and a discussion on lifestyle. 

There are no reasons to place mandatory limitations on the length of treatment.
Whether or not to continue therapy should be decided at the discretion of the well-informed hormone user and her health professional, dependent upon the specific goals and an objective estimation of benefits and risks. 

Dosage should be titrated to the lowest effective dose. Lower doses of HT than have been used routinely can maintain quality of life in a large proportion of users. Long-term data on lower doses regarding fracture risk and cardiovascular implications are still lacking. 

In general, progestogen should be added to systemic estrogen for all women with a uterus to prevent endometrial hyperplasia and cancer. However, natural progesterone and some progestogens have specific beneficial effects that could justify their use besides the expected actions on do not require progestogen co-medication. Direct delivery of progestogen to the endometrial cavity from the vagina or by an intrauterine system is logical and may minimize systemic effects. 

Androgen replacement should be reserved for women with clinical signs and symptoms of androgen insufficiency. In women with bilateral oophorectomy or adrenal failure, androgen replacement has significant beneficial effects, in particular on health-related quality of life and sexual function.

So, there you are in one fell swoop: no arbitrary end limit, individualization and lifestyle as important, need for HRT by younger women, goal-driven use, progesterone uses beyond the uterus, vaginal estrogen support, androgen use supported and defined—the whole thing. This is, to put it simply, very very useful.

Every one of you who has been stymied in the things you've asked for can print this out and take it to your doctor and suggest that perhaps he might find it useful to review the latest guidelines from this very conservative group. In fact, go whole-hog and take along the Endocrinologists' Society guidelines too! These two remarkable documents do more to provide us with unassailable foundations for meeting our needs than any of us would have dared hope just a few years ago.

The recommendations provide a very good discussion of risks and benefits. In particular, the discussion of breast cancer risk is very concrete and clearly points out the soft spots in many of the "scare" studies, such as the fact that the majority of the WHI participants were obese as well as over age 63—things that are independent risk factors for many of the negative effects attributed to HRTs in the initial analyses. It is also very specific about how (and by which estrogens and progestogens) breast cancer is stimulated.
For those here worried about being "late starters," the recommendations point, as we have in our discussions, to the lowered CV risk posed by transdermals and low doses.

There is acknowledgment that some drug regimens may help with hot flashes, but that additional work on risks is needed in order to compare those drugs to HRTs in terms of overall risk. This is very important for those whose doctors are frightened of HRT risks but assert that drug risks are trivial—something we have viewed with skepticism all along.

On the topic of compounded blends, the initial look is negative:

There are no medical or scientific reasons to recommend unregistered `bioidentical hormones'. The measurement of hormone levels in the saliva is not clinically useful. These `customized' hormonal preparations have not been tested in studies and their purity and risks are unknown.

But in fact this is, aside from the saliva testing disregard (which we're afraid we have to agree with for reasons posted elsewhere in some detail), this is actually a dazzlingly neutral stance considering the strong anti-compounding lobbying the pharmaceutical manufacturers are carrying out in conjunction with the medical insurance companies. Failure to condemn them holds the door open to possible future endorsement once ("if" is actually the more likely situation, considering the funding of research being primarily provided by pharmaceutical companies) more targeted research is performed. This is, again, more positive than we might have expected from this group and the overtly political process that forging such a public statement involves.

The rest of the document is a set of bullet points on specific symptoms, systems, and recommendations. These are all in really quite readable text with a minimum of medical terminology. The osteoporosis section, for example, recommends 700 IU of vitamin D daily in addition to calcium. That's an encouragingly updated figure from an authoritative and conservative source, for those looking to feel supported in moving their dose up beyond the old US FDA standard of 400 IU.

Basically, this ticks through every system and records, clearly, the findings of research and how they pertain to practice. It is very clear on the benefits of HRTs and how to minimize the risks (repeated emphasis, for example, on where transdermals differ from orals).

Oh, and we can't resist quoting this, for those of you whose doctors have insisted that you are just crazy when you complain of brain fog and memory loss:

New results from recent in vivo randomized, controlled neuroimaging experiments demonstrate that, in young females and those in midlife:

•  brain function is modulated by normal variation in ovarian function;
•  acute loss of ovarian hormones increases neuronal membrane breakdown;
•  acute suppression of ovarian function is associated with reduced activation of brain regions critical to memory.

So go, download and read this through. If you want the current state of the art thinking on hormones and HRTs, this is pretty much it.

NEWS: testosterone alone is not enough to provide for libido

"Testosterone cream fails as sex drive booster" is the title of a Reuters press release that caught our eye. A copy of the full study article is available from the Journal of the National Cancer Institute, which published it.

The study is a small one and deals with women who are not taking HRT. They found that testosterone cream in a dose of 10mg (!) daily for four weeks did not restore libido despite rising serum levels of the hormone. The press release goes on to say:

It's likely, Barton and her colleagues conclude, that a woman must have adequate levels of estrogen in order for testosterone to be an effective treatment for low libido.

In a related discussion in the editorial section of the Journal of the National Cancer Institute, the authors (of the editorial) note that some 31% of the study participants were taking an aromatase inhibitor, which might also have an effect on total hormone synthesis. While 72% of the participants had an "intact" ovary, ovarian function was not, seemingly, determined. Of sudden menopause, they go on to say,

chemotherapy-induced menopause, which is more abrupt than natural menopause and can have more profound physiologic and psychologic manifestations

This article also reports the results in interesting detail:

The negative results from this study are clearly stated for the primary endpoint of libido (desire/interest) as well as the secondary endpoints of mood, vitality, sexual pleasure, and total sexual functioning. The authors report no statistically significant improvement with treatment compared with placebo for any of these endpoints. Biologic measures that paralleled the questionnaire data from this study revealed statistically significant increases in bioavailable, free, and total testosterone in the treated group, and no changes in serum estrogen, sex hormone–binding globulin, or serum aspartate aminotransferase. These findings suggest that transdermal treatment with 2% testosterone did lead to measurable changes in testosterone levels and that in this short-term study there were no adverse effects on estrogen levels or liver function tests. However, between baseline and 8 weeks of follow-up, both groups showed improvement in almost all the outcome measures, although not differentially by treatment condition, suggesting that there was a large placebo effect in this study sample. Such an effect is consistent with a developing body of neuroscience research on the placebo response, demonstrating direct actions of the placebo on the brain and then subsequent effects on the body such as alleviation of pain or other symptoms.

The authors go on to acknowledge the importance of estrogen in libido, both with respect to vaginal atrophy and in supporting other sensations related to desire. This is exactly the position suggested by the Endocrinologists' Society guidelines (free signup required to read), which also state that estrogen must be brought up to normative levels as the fundamental first step before testosterone can even be reliably evaluated.

Does this conflict with the assertion that in estrogen deficiency testosterone is likely to just be used as an estrogen source? No, that data is fairly clear, as is the risk for women with estrogen-sensitive cancers in taking testosterone. We suspect that in this case the testosterone was simply inadequate to provide that foundation level of estrogen, and so the overall hormone need situation was not especially improved by its use. It's also unclear the extent to which the hormonal therapies for their cancers were affecting both the ability to produce and to synthesize estrogen from other hormones.

What's the takeaway for those of us who are not involved with cancer? I think that the lesson here is clear for all of us in common: testosterone is not a simple remedy for libido loss. This adds to the body of evidence that points to estrogen as the foundation of libido, and that, in practical terms, we must address this deficiency before we can look to adding testosterone as a magic bandaid, however appealing that this may look in simplistic terms.

And, as the editors and authors cited here note, testosterone's risks in women remain very poorly defined. The fact that there is not a lot of information out there pertaining to testosterone's risks for us does not mean that no risks exist, although for those who get their health guidance from CNN, that may certainly appear to be the case. The list of "side effects" of licensed testosterone products does not constitute research into total risks, nor do symptom lists constitute an evaluation of the underlying processes. We simply do not have strong, reliable, large-population, controlled research into how testosterone functions in women and what risks go along with its supplementation.

Does all of this mean we are against all use of testosterone? Not at all. But we are, as we are with any hormone or HRT, strongly against use based on simplistic binary criteria with a poor acknowledgment of risks: wishful thinking is not realistically safe menopausal strategy, and in such highly-loaded stakes as sexual function, we are especially vulnerable to just that danger.

Based on our present, limited state of knowledge, it does make sense that estrogen needs are what we should address as our foundation, and that only after we have seen effective estrogen support to be achieved can we begin to explore other forms of support, one of which may be testosterone. We don't feel that testosterone is "the answer" to libido, although it may be part of the complex factors that contribute to it. And we certainly don't feel that testosterone is "safe" any more than we feel that any hormone, powerful compounds that they are by their very nature, is "safe."