Paola Albertazzi

Critical review of health effects of soyabean phyto-oestrogens in post-menopausal women

A consensus view of soyabean phyto-oestrogens in clinical interventions in post-menopausal women is presented that is based on data from the EU-funded project Phytohealth. The phyto-oestrogens, primarily genistein and daidzein, were given as soyabean-protein isolates, whole-soyabean foods or extracts, supplements or pure compounds. A comprehensive literature search was conducted with well-defined inclusion or exclusion criteria. For areas for which substantial research exists only placebo-controlled double-blind randomised controlled trials (RCT) conducted on healthy post-menopausal women were included. For emerging areas all available human studies in post-menopausal women were reviewed. In order to make cross comparisons between studies the doses of isoflavones were calculated as aglycone equivalents. There is a suggestion, but no conclusive evidence, that isoflavones from the sources studied so far have a beneficial effect on bone health. The consumption of whole-soyabean foods and soyabean-protein isolates has some beneficial effects on lipid markers of cardiovascular risk. The consumption of isolated isoflavones does not affect blood lipid levels or blood pressure, although it may improve endothelial function. For menopausal symptoms there is currently limited evidence that soyabean-protein isolates, soyabean foods or red-clover (Trifolium pratense L.) extract are effective but soyabean isoflavone extracts may be effective in reducing hot flushes. There are too few RCT studies to reach conclusions on the effects of isoflavones on breast cancer, colon cancer, diabetes or cognitive function. The health benefits of soyabean phyto-oestrogens in healthy post-menopausal women are subtle and even some well-designed studies do not show protective effects. Future studies should focus on high-risk post-menopausal women, especially in the areas of diabetes, CVD, breast cancer and bone health.

Tibolone: a review

Tibolone appears to be at least as efficacious as other forms of hormonal replacement therapy (HRT) on climacteric symptoms. It does not cause withdrawal bleeding when used in women with at least 1 year of amenorrhea. It is, therefore, not indicated in perimenopause because it may cause irregular bleeding. The androgenic action of tibolone may have a two-fold benefit: on the one hand, it may help depression and libido more than other forms of HRT, while, on the other hand, it may improve some lipid parameters such as Lp(a), and triglycerides. However, this androgenic action, may also be responsible for the reduction of HDL cholesterol, that may thus reduce the beneficial effect of tibolone on lipids. It is estimated that only 30% of cardiovascular risk protection of HRT is due to improvement of classical lipids parameters while a great role is played by the direct effect of estrogen on vessels. Tibolone, as well as estrogen, has been shown to induce peripheral vasodilatation and also has a direct effect on vascular reactivity thus increasing peripheral blood flow with no changes in blood pressure or cardiac output. Tibolone seems to exert a similar effect as other forms of HRT on markers of bone metabolism and bone mass, but no data is yet available on fracture prevention.

The nature and utility of the phytoestrogens: a review of the evidence

Non-prescription remedies are becoming increasingly popular particularly amongst postmenopausal who in this market are the largest consumers. Phytoestrogens are a large family of plant derived molecules possessing various degrees oestrogen like activity. Food or food supplements containing phytoestrogen are often been advocated as an alternative to hormonal replacement therapy (HRT) in women with contraindications to the use of conventional oestrogen replacement, or simply wanting a more natural alternatives. There have been several studies performed with phytoestrogen in various aspects of the postmenopausal women health. Results have been sometimes conflicting and difficult to interpret. The lack of knowledge of what precisely is the active ingredient, its minimally effective doses, the lack of standardisation of the preparations used as well as the large individual variability of metabolism of precursors introduced with the diet may all have played a role in confusing the issue about effectiveness of these compounds. Phytoestrogen fall in the gray area between food and drugs hence in spite of the vast public interest, there are no interests in company producing these supplements in investing in research from which they will not exclusively benefit from. It is difficult for the physician to know how to advise patients on this matter. In this paper we critically review the clinical data available to date in an attempt to answer some of the most commonly asked questions about dose and type of phytoestrogens supplementation most likely to be effective in different aspects of climacteric woman health.

Polyunsaturated fatty acids. Is there a role in postmenopausal osteoporosis prevention

OBJECTIVEnTo review the effect of a diet supplemented with polyunsaturated fatty acids (PUFA) on prevention or treatment of osteoporosis.nnnMETHODSnMEDLINE (1966-April 2001), Allied Complementary Medicine (1985-2001), Cochrane Library and Database of Systematic Reviews (1st Quarter 2001) was searched. Five reviews and no systematic reviews were found on this topic in the Cochrane Library. Eleven relevant in-vivo studies were identified on the effect of these compounds on bone. Eight were animal studies and three were randomised control trials (RCT) in human.nnnRESULTSnThere are two classes of PUFA designated as n-3 and n-6 with alpha-linolenic acid (ALA). These two different types of PUFA differently influence prostaglandin formation and hence modulate bone metabolism differently. These are several in vitro and animal data suggesting that diet with a low n-6/n-3 ratio may have beneficial effects on bone mineral density. Only three, short-term, small studies have been performed in human so far. Two studies, one performed with bone markers and one with bone density showed a positive effect of PUFA on bone. While a third study showed no effect.nnnCONCLUSIONSnPreliminary, data have suggested that a diet with a low n-6/n-3 ratio may have beneficial effects on bone mineral density. Further studies are, however, required to fully assess the dose and type of PUFA to be used for optimum bone effects. This may be useful particularly for the prevention of disease in the elderly, since a diet rich in n-3 PUFA has been shown to have additional benefit on the cardiovascular, central nervous system and joints.

The effect of tibolone versus continuous combined norethisterone acetate and oestradiol on memory, libido and mood of postmenopausal women: a pilot study

OBJECTIVEnSeveral studies have shown a positive effect of oestrogen on memory, mood and well-being but these data are controversial and focus particularly on the effect of oestrogen alone. In this pilot study we have investigated the effect of a continuous combination of norethisterone acetate 1 mg and oestradiol valerate 2 mg (Kliogest) versus tibolone (Livial) on memory, sexuality and mood.nnnMETHODSnTwenty-two postmenopausal women, age range 51-57, were randomised to a 6 months single blind interventional study treatment with either continuous combined oestradiol plus norethisterone acetate, or tibolone. Computerised psychological test of memory, mood and libido were administered both before and at the end of the 6 months treatment.nnnRESULTSnFourteen patients completed the study; eight on Livial and six on Kliogest. Recognition memory was improved by Kliogest but not by Livial (P<0.05) while either drug equally improved both the reaction time (P<0.01) and accuracy of performance (P<0.001) of categorical semantic memory. Both the treatments improved libido significantly (P<0.05), while the mood did not change with either.nnnCONCLUSIONnThe results suggest that both these forms of hormonal replacement therapy improve the efficiency of memory performance and libido. However, a combination of oestradiol and norethisterone acetate seems to be marginally more effective on improving cognitive processes.

Exploration of cyclical changes in memory and mood in postmenopausal women taking sequential combined oestrogen and progestogen preparations

Objective To investigate the effect of progesterone on cognitive function, mood, sleep quality and libido when added to oestrogen in sequential combined hormonal replacement therapy regimens.

Noradrenergic and serotonergic modulation to treat vasomotor symptoms

Hot flushes are a major clinical problem for many menopausal women. Their aetiology is unknown. Centrally acting neurotransmitters are involved, but this involvement is yet to be fully characterized. In clinical trials with optimal patient selection and compliance, estrogen can reduce the frequency of hot flushes by 70–80%, and placebo by 20–40%. For some women, however, there are contraindications to the use of estrogen, and others are unwilling to use it. Furthermore, hot flushes may persist in spite of adequate estrogen replacement, and to improve symptoms physicians then have either to add another drug to the regimen or find an alternative to estrogen. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as the selective serotonin reuptake inhibitors. These reduce the frequency of hot flushes by 60%. The mechanism of this effect appears to differ from that underlying their effect on mood. They are generally well tolerated and rates of adverse events are far lower than those reported in studies of the use of these agents for depression. The limited efficacy of clonidine suggests that adrenergic mechanisms may be involved and data are awaited for more specific selective noradrenaline reuptake inhibitors. Thus, non-hormonal treatments are not as effective as estrogens in relieving hot flushes but may have a place as an alternative.

Gabapentin for the management of hot flushes: a case series.

ObjectiveTo audit the effectiveness of the anticonvulsant gabapentin on hot flushes in postmenopausal women. DesignThis was an open case series involving 11 postmenopausal women who were willing to take gabapentin for the relief of their hot flushes and were willing to keep a diary recording the number and intensity of their hot flushes, both before and during treatment. Gabapentin was started at a dose of 300 mg, to be taken at night, and the women were instructed to increase the dose up to 1,200 mg, according to symptom behavior. ResultsEleven women agreed to participate for on average 53.22 days (range, 2–79 days), but two discontinued participation—one before starting treatment and one after 2 days—so there are complete data sets for nine women. Gabapentin was found to be extremely effective in reducing hot flush activity (P < 0.001;Fig. 1). A significant reduction in symptoms was observed with a dose of 300 mg/day (P < 0.001). Scores on the Green Climacteric Scale were significantly improved from a mean of 25.72 (range, 12–42) to 19.25 (range, 13–31; P < 0.001). Palpitations (P = 0.001), panic attacks (P = 0.0001), mood (P = 0.023), muscle and joint pains (P = 0.021), and paresthesias and loss of sensation in the extremities (P = 0.001) were also shown to improve with treatment. ConclusionsIn the present case series, gabapentin was well tolerated and could be a valuable alternative for the treatment of hot flushes in women with contraindications to hormonal replacement therapy. It would be particularly beneficial for women in whom aches and pains and paresthesias are also a significant feature of the climacteric syndrome.

A Review of Non-Hormonal Options for the Relief of Menopausal Symptoms

The climacteric syndrome involves a variety of symptoms such as profuse sweating, insomnia, memory loss, decreased sexual drives, joint aches, and anxiety. However, amongst these symptoms, hot flashes and sweats are generally considered the hallmark and result in the majority of the medical consultations for this condition. Hot flashes are known to respond readily to placebo, which alone decreases their frequency by 20–40%. In the ideal setting of clinical trials, with optimal patient selection and compliance, estrogen therapy reduces hot flashes by about 70–80%; this is twice as effective as placebo. However, estrogen is unable to be universally used, either because of contraindications or because of an unwillingness of women to take it. Furthermore, hot flashes may persist in spite of adequate estrogen replacement, and physicians are often faced with the dilemma of finding something to administer in place of, or in addition to, estrogen to improve symptoms. The most commonly used non-hormonal alternatives for climacteric symptoms are neurotransmitter modulators such as serotonin reuptake inhibitors and gabapentin. These are, at best, approximately half as effective as estrogen for the relief of menopausal symptoms, and are only marginally better than placebo.Complementary treatment, particularly over-the-counter phytotherapeutic extracts, are very popular and women often try a variety of such products before resorting to conventional medicine. Preparations containing isoflavones, such as soy extract and red clover or extracts from evening primrose or cimicifuga (black cohosh, Actaea racemosa, syn. Cimicifuga racemosa), in variable doses are very popular for the treatment of hot flashes. The scientific support for their efficacy certainly does not equal their popularity.Non-hormonal treatments for menopause are not as effective as estrogens in relieving hot flashes, but may have a role in therapy for women who have contraindications to gonadal steroid use.

Mood swings across the menstrual cycle: a comparison between oral contraceptive users and non-users

Abstract In this study we have evaluated the cyclical mood change throughout menstrual cycle in oral contraceptive (OC) users and non-users. A total of 62 young women, with a regular menstrual cycle and not clinically depressed, kept, for five weeks, daily records of their visual analogue ratings of mood, irritability, energy and tension (Global Vigor-Affect scale). A Profile of Mood States was performed weekly as a further self-evaluation of mood. Eighteen women were taking oral contraceptives and 44 were non-users. Only the depression-dejection dimension varied significantly during the menstrual cycle (p < 0.05) with an improvement of mood around day 14 and worsening premenstrually. No significant differences were found between the two groups. On the whole the results suggest that oral contraceptives do not alter the physiological fluctuation of mood occurring with menses in young healthy women.