Menopause Treatments

Many women arrive at their menopause years without knowing anything about what they might expect, or when or how the process might happen, and how long it might take. Very often a woman has not been informed in any way about this stage of life; at least in the US, it may often be the case that she has received no information from her physician, or from her older female family members, or from her social group. In the US, there appears to be a lingering taboo which hangs over this subject.

As a result, a woman who happens to undergo a strong perimenopause with a large number of different effects, may become confused and anxious, fearing that something abnormal is happening to her. There is a strong need for more information and more education on this subject.

In January 2003, the U.S. Food and Drug Administration required Wyeth to affix a "black box" warning to PremPro, stating:

"WARNING:
Estrogens and progestins should not be used for the prevention of cardiovascular disease. The Women’s Health Initiative (WHI) reported increased risks of myocardial infarction, stroke, invasive breast cancer, pulmonary emboli, and deep vein thrombosis in postmenopausal women during 5 years of treatment with conjugated equine estrogens (0.625 mg) combined with medroxyprogesterone acetate (2.5 mg) relative to placebo (see CLINICAL PHARMACOLOGY, Clinical Studies). Other doses of conjugated estrogens and medroxyprogesterone acetate, and other combinations of estrogens and progestins were not studied in the WHI ..."

Adverse effects of conjugated equine estrogens

Women had been advised for many years by numerous doctors and drug company marketing efforts (at least in the USA) that hormone therapy with conjugated equine estrogens after menopause might reduce their risk of heart disease and prevent various aspects of aging. However, a large, randomized, controlled trial (the Women's Health Initiative) found that women undergoing HT or HRT with conjugated equine estrogens (Premarin), whether or not used in combination with a synthetic progestin (Premarin plus Provera, known as Prempro), had an increased risk of breast cancer, heart disease, stroke, and Alzheimer's disease. Although this increase in risk was small overall, it passed the thresholds that had been established by the researchers in advance as sufficient to ethically require stopping the study.

When these results were first reported in 2002, the popular media sensationalized the story and exaggerated the risk, while the manufacturer continued to attempt to minimize the degree of risk. However most news stories failed to mention that the average age of the women in WHI was 62 years old, significantly older than the time when most doctors start patients on HRT, and in fact many years into postmenopause. In order to enroll in the study, patients had to be asymptomatic of hot flashes, so they would not know whether they received the placebo. For these reasons WHI was not representative of generally accepted clinical practice.

The 2002 and 2003 announcements of the Women's Health Initiative of the American National Institute of Health and The Million Women Study of the UK Cancer Research and National Health Service collaboration respectively, that HRT treatment coincides with a increased incidence of breast cancer, heart attacks and strokes, lead to a sharp decline in HRT prescription throughout the world , which was followed by a decrease in breast cancer incidence .

On hearing the news about the WHI study, many women discontinued equine estrogens altogether, with or without their doctor's approval. The number of prescriptions written for Premarin and PremPro in the United States dropped within a year almost to half of their previous level. This sharp drop in usage was followed by large and successively larger drops in new breast cancer diagnoses, at six months, one year, and 18 months after the drop in Premarin and Prempro prescriptions, for a cumulative 15% drop by the end of 2003. However, the apparent meaning of this correlation is called into question by the fact that prescriptions of Prempro and Premarin fell dramatically in Canada as well, but no similarly dramatic drop in Canada's breast cancer rates was observed during the same time period. Studies designed to track the further progression of this trend after 2003 are under way, as well as studies designed to quantify how much of the drop was related to the reduced use of HT/HRT.

Other forms of hormone therapy

The adverse biological effects of xenoestrogens and progestins revealed by studies of Premarin and PremPro do not necessarily generalize to supplementation with human forms of estrogen and progesterone. For example, a pilot study reported in ''JAMA'' by Smith, Heckbert, et al. found clinical evidence that oral conjugated equine estrogens caused clotting, but the other estrogen compound tested in the same study, bioidentical esterified estrogens, did not. conjugated equine estrogens were found to be associated with increased venous thrombotic risk. In sharp contrast, the study found that users of esterified estrogen had no increase in venous thrombotic risk.

Because of the controversy about Premarin-based hormone therapy, a significant percentage of doctors now prescribe bioidentical hormone products to their patients who request HRT to ease their perimenopausal symptoms. Estradiol is a precursor to estrogen in the human body; sold under the brand name Estrace, estradiol products produce fewer side effects than conjugated equine estrogens. Prometrium is a bioidentical progesterone which can be used in conjunction with Estrace to produce a PremPro-like blend for women who desire or require a combined HRT (e.g. women who still have a uterus, since estrogen and estrogen precursors are known to cause uterine cancer when used without the protective qualities of progesterone). However, all hormone replacement therapies do carry some health risks, including high blood pressure, blood clots, and increased risks of breast and uterine cancers. Women who have had a hysterectomy seem to tolerate estrogen-only therapy with fewer risks than apply to mixed-HRT in women who still have a uterus.

Selective Estrogen Receptor Modulators (SERMs)

SERMs are a category of drugs, either synthetically produced or derived from a botanical source (Phytoserms), that act selectively as agonists or antagonists on the estrogen receptors throughout the body. While most SERMs are known to increase hot flushes, Femarelle decreases them. In addition to the relieving effects on menopausal symptoms, Femarelle also increases bone mass density (BMD), making it protective against osteoporotic fractures. These effects are achieved by an agonistic interaction with estrogen receptors in the brain and bone. On the other hand, an antagonist interaction with estrogen receptors in the breast and uterus, has no effect on these tissues.

Antidepressants

Antidepressants such as paroxetine (Paxil), Fluoxetine hydrochloride (Prozac), and Venlafaxine hydrochloride (Effexor) have been used with some success in the treatment of hot flashes, improving sleep, mood, and quality of life. There is a theoretical reason why SSRI antidepressants might help with memory problems—they increase circulating levels of the neurotransmitter serotonin in the brain and restore hippocampal function. Sarafem is prescribed for premenstrual dysphoric disorder (PMDD), a mood disorder often exacerbated during perimenopause and early menopause. PMDD has been found by PET scans to be accompanied by a sharp drop in serotonin in the brain, and to respond quickly and powerfully to SSRIs.

Gabapentin

Gabapentin and other GABA analogs are anti-seizure medications. Several GABA analogs are prescribed off-label for a variety of other conditions (such as pregabalin being used to treat the symptoms of fibromyalgia under the brand name Lyrica); gabapentin itself has been shown to be as effective as estrogen at reducing hot flashes.

Blood pressure medicines

Blood pressure medicines including clonidine (Catapres) are about as effective as antidepressants for hot flashes, but do not have the other mind and mood benefits of antidepressants. However they may merit special consideration by women suffering both from high blood pressure and hot flashes.

Complementary and alternative therapies

It is important to examine the claim that herbal remedies help relieve menopausal symptoms. Some botanical sources, referred to as phytoestrogens, are known to have an estrogenic effect on the body and therefore create a moderated estrogenic effect. Others, such as Femarelle, have Selective Estrogen Receptor Modulator (SERM) qualities, thereby reducing the safety risks involved in estrogenic-like treatments

In the area of complementary and alternative therapies, acupuncture treatment is promising. There are some studies indicating positive effects, especially on hot flashes

but also others showing no positive effects of acupuncture regarding menopause.

There are regular claims that soy isoflavones are beneficial concerning menopause. However, one study indicated that soy isoflavones did not improve or appreciably affect cognitive functioning in postmenopausal women.

Other remedies which work in some studies but in others appear to be no better than a placebo include red clover isoflavone extracts and black cohosh. Black cohosh can cause the stimulation of pre-existing breast cancer and liver toxicity.

Other therapies

Lack of lubrication is a common problem during and after perimenopause. Vaginal moisturizers can help women with overall dryness, and lubricants can help with lubrication difficulties that may be present during intercourse. It is worth pointing out that moisturizers and lubricants are different products for different issues: some women feel unpleasantly dry all of the time apart from during sex, and they may do better with moisturizers all of the time. Those who need only lubricants are fine just using the lubrication products during intercourse.

Low-dose prescription vaginal estrogen products such as estrogen creams are generally a safe way to use estrogen topically, in order to help vaginal thinning and dryness problems (see vaginal atrophy) while only minimally increasing the levels of estrogen in the bloodstream.

In terms of managing hot flashes, lifestyle measures, such as drinking cold liquids, staying in cool rooms, using fans, removing excess clothing layers when a hot flash strikes, and avoiding hot flash triggers such as hot drinks, spicy foods, etc, may partially supplement (or even obviate) the use of medications for some women.

Individual counseling or support groups can sometimes be helpful to handle sad, depressed, anxious or confused feelings women may be having as they pass through what can be for some a very challenging transition time.