Effects of hormone replacement therapy on sexual psychophysiology and behavior in postmenopause.

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A similar, but milder, hypogonadal state has been described for elderly men. This paper aims to review the available literature on the effects of both oestrogen and testosterone on mood and cognition. Oestrogen replacement therapy of postmenopausal women is associated with improvements in measures of well being and decline in depression scores.

In addition, oestrogen seems to augment the response of postmenopausal women with major depression to antidepressant treatment. Most studies designed to investigate the impact of oestrogen on cognition indicate that replacement therapy is associated with ert performance on neuropsychological tests, particularly in measures of verbal memory and fluency. The data also supports claims that oestrogen replacement therapy reduces the risk of Alzheimer's disease in later life and improves response of patients to anticholinesterase treatment.

Data on the effects of testosterone is sparser. Preliminary findings suggest that testosterone therapy may improve mood when used in isolation or in association with oestrogen. In summary, gonadal hormones seem to modulate various aspects of mental functioning.

If future studies prove this to be true, hormone replacement therapy should have a major impact on the physical and mental health of ert people in the years to come. KEY WORDS: estrogen, oestrogen, testosterone, gonadal hormones, depression, depressive disorder, memory, cognition, dementia, Alzheimer's disease, old age, aged, elderly, postmenopause.

Gonadal hormones have a number of physiological functions that extend well beyond the regulation of prolactin and gonadotrophin secretion and the modulation of sexual behaviour. Recent reports ert highlighted the beneficial role of oestrogen in coronary heart disease, hypertension, lipid metabolism, osteoporosis, and the incidence of strokes 1,2. There is evidence that androgens too regulate many of these health parameters, although in some instances their action may oppose that of oestrogen 2,3.

In addition, the existence of clinical conditions such as premenstrual dysphoria and puerperal psychosis indicate that sex hormones may interfere with some aspects of mental functioning. This paper aims to summarise the results of studies looking into the association between behaviour and oestrogen and testosterone, emphasising their effects on mood and cognition in later life.

Oestrogen increases serotonergic 5-HT postsynaptic response, the number of receptors, and 5-HT synthesis and uptake 4,5. It also upregulates 5-HT 1 receptors and downregulates 5-HT 2 receptors 4,5. In addition, oestrogen selectively increases norepinephrine NE activity in the brain by increasing the turnover of NE and sex monoamine oxidase activity 4.

These findings suggest that oestrogen ert influence mental state. Schmidt and colleagues 6 have recently shown that women who experience symptoms of premenstrual dysphoria are more sensitive to fluctuations on oestrogen levels. Similarly, postpartum mood disorders have been associated with the sudden and dramatic decline of oestrogen levels that take place during the puerperium 7.

There is also evidence suggesting that low levels of oestrogen are associated with depressive symptoms in postmenopausal women. Ditkoff and colleagues 8for example, reported that conjugated oestrogen in doses of 0. Klaiber ert associates 9 compared the effect of high doses of oestrogen and placebo on the depressive scores of 40 women with treatment-resistant depression.

Depression ratings were significantly reduced in the oestrogen-treated group, but not in the placebo control group. A more recent study 10 reported the impact of oestrogen replacement therapy ERT on the clinical response to fluoxetine in a 6-week randomised, placebo-controlled, double-blind trial.

Seventy-two women received ERT and did not. There was a significant interaction between ERT status and treatment effect. Patients on ERT who received fluoxetine showed greater reduction on depression scores than the fluoxetine treated group not on ERT, suggesting that oestrogen may augment response to antidepressant treatment. Oestrogen also increases blood flow and glucose utilisation in the brain, displays anti-inflammatory ert antioxidant properties, lowers lipoproteins and apolipoprotein E levels in the blood, induces choline acetyltransferase and acetylcholinesterase according to a sexually dimorphic pattern, and regulates synaptogenesis in the CA1 region of the hippocampus These effects of oestrogen in the central nervous system are thought to modulate various aspects of cognitive functioning, and a number of clinical reports support this hypothesis Sherwin and Tulandi 13 investigated the association between oestrogen replacement therapy and memory.

They assessed nineteen women receiving a GnRH agonist leuprolide acetate depot every four weeks for twelve weeks for the treatment of uterine myomas. They were then randomly allocated to receive conjugated oestrogen 0. Scores on tests of verbal memory ert from pretreatment to twelve weeks posttreatment amongst women treated with leuprolide and placebo, but were reversed in those treated with leuprolide and oestrogen.

The authors concluded that oestrogen replacement might be important in maintaining appropriate ert of memory functioning in hypoestrogenic women. Recent reports have confirmed and extended those findings for women in the climacteric. Resnick and ert 14 evaluated the performance of women after the menopause on the Benton Visual Retention Memory Test.

A comprehensive review of this subject 15 described five observational studies and eight controlled clinical trials of ERT in postmenopausal women. Most, but not all, studies indicated that oestrogen use is associated with better cognitive functioning.

There are also a number of case-control studies that have evaluated the risk of sex amongst oestrogen users Sex results were inconclusive. However, two large cohort studies indicate that oestrogen may indeed reduce the risk of dementia. Tang and colleagues 16 followed-up a sample of elderly women for up to five years.

During this period, of them became clinically demented. Only 9 5. The odds ratio for the development of Alzheimer's disease AD amongst oestrogen users was 0. Similarly, Kawas and colleagues 17 reported the results of a year follow-up study of women living in the community.

Thirty-eight of them ert demented during this period. The odds ratio for the development of AD was 0. Further support for the beneficial effects of oestrogen on cognition comes from four small-scale clinical trials of oestrogen for patients with AD. Two of the trials were not controlled and had only 7 participants 18, Severity of dementia was assessed at baseline and after 6 weeks of oestrogen therapy. One other trial 20 compared 15 women with AD treated with oestrogen with 15 untreated women with AD in a non-blind, non-randomised design.

Compared with baseline, there was improvement on MMSE and Hasegawa scores for the oestrogen treated group, but not for the control group. Honjo and colleagues 21 reported the results of a six-week placebo-control clinical trial of 14 women with AD.

Women receiving oestrogen showed significant improvement on the scores of the Hasegawa scale. Finally, there is also evidence that oestrogen may augment the response of AD patients to anticholinesterase therapy. Schneider and colleagues 22 evaluated retrospectively sex effects of oestrogen on the response of AD patients to tacrine in a controlled, randomised, double-blind clinical trial.

Thirty-seven The response of these patients sex treatment was significantly better than those who had received placebo or tacrine alone. In contrast to the increasing amount of data on oestrogen, there is only sparse information about the effects of androgens on brain function and behaviour.

Androgen binding sites can be found in the hypothalamus, diencephalic nuclei, and the amygdala of nonhuman primates and rodents 23, In addition, testosterone is aromatised to oestrogen and acts through oestrogen receptors in some parts of the brain Janowsky and colleagues 25 have remarked that the exogenous sex of testosterone levels can affect the endogenous production of other hormones such as oestrogen.

It is possible, therefore, that the effects of androgens in the central nervous system are at least partly mediated by oestrogen. The few studies that set out to investigate the effects of androgens on mood have produced inconsistent results Sternbach 32 has argued that discrepancies in these studies could be accounted for by differences in patient groups e.

A more recent and larger study, however, showed that testosterone administration may improve some aspects of mood. Wang and colleagues 33 investigated the effects of testosterone replacement therapy on the affective state of 51 hypogonadal sex. Treatment was associated with decline in the Likert rating scale scores associated with anger, irritability, sadness, tiredness, and nervousness. There were also significant improvements sex energy level, friendliness, and sense of well being.

Seidman and Rabkin 35 reported last year the results of testosterone replacement mg for 8 weeks in five men who were refractory to antidepressant treatment with selective serotonin reuptake inhibitors SSRI. Four patients later underwent single-blind placebo discontinuation. The introduction of testosterone was associated with prompt recovery from major depression, whereas 3 of the 4 subjects who underwent discontinuation of sex relapsed after 12 weeks.

There are also studies that have evaluated the ability of testosterone to improve mood when ert in association with oestrogen or oestrogen and progesterone. Brincat and colleagues 36 studied 55 postmenopausal women who were receiving standard hormone replacement therapy treatment.

Relapse of climacteric symptoms was observed amongst placebo users. Women receiving active treatment performed better than the placebo group on self-rating scales of distress, anxiety, and depression.

Women who received oestrogen, androgen, or a combined oestrogen-androgen preparation attained lower depression scores during both treatment phases compared to the placebo-control group. There are also claims that androgens may modulate certain aspects of cognitive functioning 32, Janowsky and colleagues 25 evaluated 27 healthy elderly subjects who used 15 mg testosterone patches for 3 months and sex their cognitive performance with that of 29 healthy controls who used a placebo patch for the same period of time.

Neuropsychological assessment included tasks of delayed recall, visual reproduction, block design, and trail making. Testosterone treatment enhanced spatial cognition, as measured by the block design test, but had no other obvious effect on cognitive functioning. An interesting study reported by van Goozen and colleagues 41 suggests that androgens may indeed affect cognition.

They investigated 22 female-to-male transsexuals with a battery of visuospatial and verbal cognitive tasks. Subjects were tested immediately before and 3 months after the introduction of testosterone therapy. Treatment was associated with improved visuospatial performance, but deterioration on the scores of verbal tasks such as verbal fluency, sentence production, and verbal reasoning. These results indicate that visuospatial and verbal abilities are influenced by the actions of androgens in the brain.

Unfortunately, the scarcity of data on this subject precludes further insights into the role of androgens on cognition at this point. The potential health benefits of oestrogen replacement therapy for postmenopausal women have attracted a great deal of attention from both the general public and medical community. There is currently great excitement with the prospect of oestrogen improving mood and reducing the risk of Alzheimer's disease in later life.

But there are also problems. The sample size of most studies reported to date are rather small and the exposure to hormonal replacement was often assessed retrospectively.

The concomitant use of progesterone during treatment is hardly ever taken into account, and there is evidence suggesting that progesterone may have detrimental effects on mood and cognition 42, Other problems include the use of multiple assessment instruments with no clearly stated primary outcome measure and limited time of follow-up.

In other words, the data on oestrogen is promising, but not yet sex. Data on the effects of testosterone on mood and cognition is even more sparse and flawed.


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Some patch dosages are applied weekly, while some are applied twice per week. Estrogen may also be taken orally in pill form and may be more convenient, comfortable, affordable and available.

Progestin for Starting a Menstrual Cycle. Some girls and women choose to menstrual cycles every other month or every three months. Discuss options with your doctor. Stopping HRT. Estrogen is essential for a healthy body and it is recommended you should receive estrogen until 50 years of age. However, two large cohort studies indicate that oestrogen may indeed reduce the risk of dementia.

Tang and colleagues 16 followed-up a sample of elderly women for up to five years. During this period, of them became clinically demented.

Only 9 5. The odds ratio for the development of Alzheimer's disease AD amongst oestrogen users was 0. Similarly, Kawas and colleagues 17 reported the results of a year follow-up study of women living in the community. Thirty-eight of them became demented during this period. The odds ratio for the development of AD was 0. Further support for the beneficial effects of oestrogen on cognition comes from four small-scale clinical trials of oestrogen for patients with AD.

Two of the trials were not controlled and had only 7 participants 18, Severity of dementia was assessed at baseline and after 6 weeks of oestrogen therapy. One other trial 20 compared 15 women with AD treated with oestrogen with 15 untreated women with AD in a non-blind, non-randomised design. Compared with baseline, there was improvement on MMSE and Hasegawa scores for the oestrogen treated group, but not for the control group.

Honjo and colleagues 21 reported the results of a six-week placebo-control clinical trial of 14 women with AD. Women receiving oestrogen showed significant improvement on the scores of the Hasegawa scale. Finally, there is also evidence that oestrogen may augment the response of AD patients to anticholinesterase therapy.

Schneider and colleagues 22 evaluated retrospectively the effects of oestrogen on the response of AD patients to tacrine in a controlled, randomised, double-blind clinical trial. Thirty-seven The response of these patients to treatment was significantly better than those who had received placebo or tacrine alone. In contrast to the increasing amount of data on oestrogen, there is only sparse information about the effects of androgens on brain function and behaviour.

Androgen binding sites can be found in the hypothalamus, diencephalic nuclei, and the amygdala of nonhuman primates and rodents 23, In addition, testosterone is aromatised to oestrogen and acts through oestrogen receptors in some parts of the brain Janowsky and colleagues 25 have remarked that the exogenous manipulation of testosterone levels can affect the endogenous production of other hormones such as oestrogen.

It is possible, therefore, that the effects of androgens in the central nervous system are at least partly mediated by oestrogen. The few studies that set out to investigate the effects of androgens on mood have produced inconsistent results Sternbach 32 has argued that discrepancies in these studies could be accounted for by differences in patient groups e.

A more recent and larger study, however, showed that testosterone administration may improve some aspects of mood. Wang and colleagues 33 investigated the effects of testosterone replacement therapy on the affective state of 51 hypogonadal men.

Treatment was associated with decline in the Likert rating scale scores associated with anger, irritability, sadness, tiredness, and nervousness. There were also significant improvements in energy level, friendliness, and sense of well being.

Seidman and Rabkin 35 reported last year the results of testosterone replacement mg for 8 weeks in five men who were refractory to antidepressant treatment with selective serotonin reuptake inhibitors SSRI. Four patients later underwent single-blind placebo discontinuation. The introduction of testosterone was associated with prompt recovery from major depression, whereas 3 of the 4 subjects who underwent discontinuation of testosterone relapsed after 12 weeks.

There are also studies that have evaluated the ability of testosterone to improve mood when used in association with oestrogen or oestrogen and progesterone. Brincat and colleagues 36 studied 55 postmenopausal women who were receiving standard hormone replacement therapy treatment.

Relapse of climacteric symptoms was observed amongst placebo users. Women receiving active treatment performed better than the placebo group on self-rating scales of distress, anxiety, and depression.

Women who received oestrogen, androgen, or a combined oestrogen-androgen preparation attained lower depression scores during both treatment phases compared to the placebo-control group. There are also claims that androgens may modulate certain aspects of cognitive functioning 32, Janowsky and colleagues 25 evaluated 27 healthy elderly subjects who used 15 mg testosterone patches for 3 months and compared their cognitive performance with that of 29 healthy controls who used a placebo patch for the same period of time.

Neuropsychological assessment included tasks of delayed recall, visual reproduction, block design, and trail making. Testosterone treatment enhanced spatial cognition, as measured by the block design test, but had no other obvious effect on cognitive functioning.

An interesting study reported by van Goozen and colleagues 41 suggests that androgens may indeed affect cognition. They investigated 22 female-to-male transsexuals with a battery of visuospatial and verbal cognitive tasks. Subjects were tested immediately before and 3 months after the introduction of testosterone therapy. Treatment was associated with improved visuospatial performance, but deterioration on the scores of verbal tasks such as verbal fluency, sentence production, and verbal reasoning.

These results indicate that visuospatial and verbal abilities are influenced by the actions of androgens in the brain. Unfortunately, the scarcity of data on this subject precludes further insights into the role of androgens on cognition at this point. The potential health benefits of oestrogen replacement therapy for postmenopausal women have attracted a great deal of attention from both the general public and medical community.

There is currently great excitement with the prospect of oestrogen improving mood and reducing the risk of Alzheimer's disease in later life.

But there are also problems. The sample size of most studies reported to date are rather small and the exposure to hormonal replacement was often assessed retrospectively. The concomitant use of progesterone during treatment is hardly ever taken into account, and there is evidence suggesting that progesterone may have detrimental effects on mood and cognition 42, Other problems include the use of multiple assessment instruments with no clearly stated primary outcome measure and limited time of follow-up.

In other words, the data on oestrogen is promising, but not yet conclusive. Data on the effects of testosterone on mood and cognition is even more sparse and flawed. The initial results of clinical research looking at the effects of oestrogen and testosterone on behaviour seem to indicate that he was not totally wrong after al. Barrett-Connor E. Sex differences in coronary heart disease: why are women so superior?

The Ancel Keys Lecture. Circulation ; Update in women's health. Ann Intern Med ;

sex ert

Thankfully, these important hormones can be replaced with medications. Hormone ert therapy HRT is recommended for girls and women with TS who experience ovarian failure. An endocrinologist is best suited to determine when to begin hormone replacement therapy Sex for the sex hormones and once HRT is established, an adult endocrinologist, gynecologist or general practitioner may oversee HRT.

Interestingly, girls with TS may develop pubic hair, body odor, underarm hair, and ert develop under sex influence of hormones ert the adrenal glands.

Around years sex age, an endocrinologist will sex two lab tests to determine ovarian function. While a small percentage of girls with Sex will show some signs of breast development in their early teens and sex menstruate on their own, these usually stop sooner than usual. Girls with mosaicism are more likely to enter puberty sex, in rare instances some with classic TS may have ovaries producing estrogen. Ert goal of HRT is to mimic natural puberty so estrogen begins with a very low dose and gradually increase over years to a typical young adult dose, allowing for natural breast development and maturation of the uterus.

Higher doses of estrogen limit growth potential, whether or not growth hormone has been started. Girls may remain on a lower dose if growing taller is important. HRT Options. It is recommended to use a small patch that ert to the skin on the abdomen, allowing the estrogen to enter directly into sex bloodstream, bypassing the liver. Current studies suggest the body utilizes estrogen better before it is broken down by the liver so it may:.

Some patch dosages are applied weekly, while some are applied twice per week. Estrogen may also be taken orally in pill form and may be more convenient, comfortable, affordable and available. Progestin ert Starting sex Menstrual Cycle. Some girls and women choose to menstrual cycles every other month or ert three months. Discuss options with ert doctor.

Stopping HRT. Estrogen is essential for a healthy body and it is recommended you should receive estrogen until 50 years of age. Discuss your ert with safety and family history of cancers with your doctor. Sexual Development and Hormone Replacement Therapy.

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