Evaluation of mammographic density and (99m)Tc-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy

OBJECTIVE: To evaluate changes in mammographic density and (99m)Tc-sestamibi scintimammographic uptake in postmenopausal women on hormone replacement therapy (HRT). METHODS: Seventy-five postmenopausal women were prospectively studied and allocated into three groups: 50 women were randomized to either Group 1 (G1, n=25), which received 2mg of 17beta-oestradiol continuously combined with 1mg of norethisterone acetate (E2/NETA, Kliogest, Medley) or Group 2 (G2), which received 2.5mg/day of tibolone (Livial, Organon). The remaining 25 women, who were asymptomatic and had no desire to undergo HRT, constituted the control group (G3). Each patient was submitted to both mammography and scintimammography at baseline and after six months. Mammographic density was evaluated by using the BI-RADS classification system. The classification system of Barros et al. was used in the interpretation of scintimammography. For statistical analysis, the Chi-square test, ANOVA and Pearson's correlation were used. RESULTS: At six months, increased mammographic density was observed in 48% of G1, 12% of G2 and 16% of G3 patients (p<0.001). The increase in sestamibi uptake was 56% in G1, 28% in G2 and 24% in G3 (p<0.001). Increases in both density and uptake were significantly higher in the group on E2/NETA than among tibolone users and the controls. CONCLUSION: In postmenopausal women, HRT with E2/NETA was associated with increased mammographic density and increased (99m)Tc-sestamibi scintimammographic uptakes, suggesting greater mithochondrial activity in the cells of the mammary duct. This was not observed in users of 2.5 mg of tibolone, demonstrating that the effects on the breast were reduced. The same was observed in the control group.     

Physical activity and mammographic parenchymal patterns among Greek postmenopausal women

Objective

To examine whether physical activity during the last five years is related to later breast mammographic density in postmenopausal Greek women.

Methods

We designed a cross-sectional study in 724 women, of ages 45–67 years. An interview-administered questionnaire was used to obtain information on duration and intensity of recreational physical activity during five years preceding study recruitment. Mammograms were evaluated according to BIRADS classification and BIRADS score was also estimated. Multivariate ordinal logistic regression analysis was used to assess associations between physical activity index and breast density according to the BIRADS classification methods.

Results

We observed a statistically significant inverse association of mammographic breast density measured by the BIRADS classification method and recreational exercise (OR = −0.10; 95% CI −0.018, −0.001; p = 0.022). For one unit increase in physical activity as expressed by the MET-h/week score, the odds of lower versus higher breast density categories are 1.105 greater, given that all of the other variables in the model are held constant. A modifying effect by age at recruitment was evident among participants, with a stronger inverse association between recreational activity and mammographic breast density among older women (OR = −0.036; 95% CI −0.063, −0.009; p = 0.009). An inverse association between physical activity and BIRADS score was evident, not reaching statistical significance (OR = 0.00; 95% CI −0.009, 0.008; p = 0.887).

Conclusions

Mammographic breast area was lower in postmenopausal women who participated in sports/recreational physical activity compared to inactive controls. Increasing physical activity levels among postmenopausal women might be a reasonable approach to reduce mammographic density. However, until more physical activity and mammographic breast density studies are conducted that confirm our findings, they have to be interpreted with caution, due to the retrospective nature of our data and the possibility of memory bias.     

A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.

OBJECTIVE: Our purpose was to investigate the effect of tibolone in a prospective randomized, double-blind pilot study in postmenopausal women with clinically palpable mastopathic changes. METHODS: Twenty postmenopausal non-users of hormone replacement therapy undergoing mammography were randomly allocated to receive either 2.5 mg tibolone (Livial, Organon) or placebo (2 mg lactose). Mammographic density according to the Wolfe classification, severity of breast discomfort, parity, smoking habits, body weight and follicle-stimulating hormone (FSH) and estradiol (E(2)) levels were documented at baseline and after 6 months of treatment. RESULTS: There were no statistically significant differences between the two treatment groups in terms of parity, smoking, body weight and FSH and E(2) levels. At 6 months, four patients in the tibolone group showed reduced breast density, compared with one patient in the placebo group. Whereas no significant differences were found between the two treatment groups when the categories 'minimal reduction' and 'reduction' in mammographic density were combined, combination of the categories 'no change' and 'minimal reduction' showed a significant difference (P<0.036). Also, women in the tibolone group showed a statistically significant improvement in breast discomfort (P<0.019). CONCLUSION: This pilot study showed decreases in breast density as well as an attendant significant alleviation of breast discomfort in women with baseline mastopathic changes treated with tibolone for 6 months, which may be due to the inhibitory effect of tibolone on the enzymes involved in the biosynthesis of estradiol demonstrated in previous trials and should be further evaluated in long-term studies.     

Effects of black cohosh on the plasminogen activator system in vascular smooth muscle cells

Objective

The rhizome of the Cimicifuga racemosa plant (commonly known as black cohosh) has been used for menopausal complaints. Studies regarding the cardiovascular effects of black cohosh are lacking. We investigated the effect of black cohosh on the plasminogen activator system in cultured vascular smooth muscle cells (VSMCs).

Methods

VSMCs were isolated from rat aortae. Expression of plasminogen activator inhibitor type 1 (PAI-1) and tissue-type plasminogen activator (t-PA) proteins were evaluated by Western blot analysis and enzyme-linked immunosorbent assay, respectively. The activities of PAI-1 and t-PA in the conditioned media were assessed by fibrin overlay zymography. A 40% 2-propanol extract of black cohosh was used.

Results

Black cohosh extract (BcEx) stimulated the protein expression of PAI-1, but it did not affect that of t-PA. Vitamin E, a potent antioxidant, inhibited the BcEx-induced increase in PAI-1 expression, while ICI 182,780, an estrogen receptor antagonist, had no effect. Fibrin overlay zymography revealed that BcEx increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA by inducing a binding to PAI-1.

Conclusions

BcEx induces PAI-1 protein expression in the VSMCs likely via an oxidant mechanism. It also stimulates the enzyme activity of PAI-1 and reduces that of free t-PA. These findings suggest that black cohosh might exert a negative influence on fibrinolysis.     

Impact on uterine bleeding and endometrial thickness: tibolone compared with continuous combined estradiol and norethisterone acetate replacement therapy

Objective: To evaluate endometrial thickness and the incidence of uterine bleeding in postmenopausal women using either tibolone 2.5 mg or continuous combined 2 mg estradiol and 1 mg norethisterone acetate (E+NETA) daily as hormone replacement therapy. DESIGN: We compared diary records of self-reported uterine bleeding and measurements of endometrial thickness, area, and volume by transvaginal sonography at baseline and after 1, 3, 6, and 12 months in a 1-year, prospective, randomized, double-blind, single-center trial of 100 postmenopausal women aged 46-69 years. Bleeding frequencies and endometrial thickness were assessed by Chi-square tests and analysis of covariance, respectively. RESULTS: Self-reported bleeding was significantly less in the tibolone group. Bleeding episodes were reported by 27.7% of women in the tibolone group and by 59.2% in the E+NETA group. The mean number of days with bleeding was 5.8 +/- 27.0 in the tibolone group and 35.6 +/- 58.6 in the E+NETA group. Six women in the tibolone group and seven in the E+NETA group discontinued the study; three in the E+NETA group because of bleeding. The mean endometrial thickness at baseline was 2.56 +/- 0.81 mm in the tibolone group and 2.58 +/- 1.04 mm in the E+NETA group. After 1 year, the corresponding figures were 3.32 +/- 1.58 mm and 3.07 +/- 1.68 mm. Thus, 86% of women in the tibolone group and 93% in the E+NETA group had an endometrial thickness of less than 5 mm. CONCLUSIONS: Use of tibolone 2.5 mg daily for 1 year was associated with significantly less bleeding and spotting compared with daily continuous combined 2 mg estradiol and 1 mg norethisterone acetate in postmenopausal women in the presence of both minimal and nonprogressive increase of endometrial thickness associated with the two regimens.     

Tibolone: clinical recommendations and practical guidelines. A report of the International Tibolone Consensus Group

An international multidisciplinary panel of experts in the management of the menopause met at the 4th Amsterdam Menopause Symposium in October 2004 to determine the specific place of tibolone, a synthetic steroid with a unique clinical profile, within the wide range of currently available postmenopausal therapy options. The consensus was that tibolone is a valuable treatment option for women with climacteric complaints. As well as relieving vasomotor symptoms, tibolone has positive effects on sexual well-being and mood, and improves vaginal atrophy and urogenital symptoms. Prevention of bone loss with tibolone is comparable to that seen with estrogen therapy (ET) and estrogen/progestogen therapy (EPT). As tibolone rarely causes endometrial proliferation, no additional progestogen is required. It also has good tolerability, being associated with a low incidence of vaginal bleeding and of breast pain. Tibolone does not increase mammographic density. Absolute numbers of women at increased risk for breast cancer are estimated to be low or absent with both tibolone and ET, and the risk with tibolone should be significantly lower than that with EPT. Tibolone might therefore be preferable to EPT in certain women who have not been hysterectomised. Based on the evidence available, the panel proposed a number of subgroups of postmenopausal women with vasomotor symptoms in whom tibolone might have added value; these included women with sexual dysfunction, mood disorders, fibroids and urogenital complaints, as well as those with breast tenderness or high mammographic breast density with EPT use.     

Safety of herbal medicinal products in women with breast cancer

Objective

To review and summarise current evidence on the efficacy and safety of herbal medicinal products for the relief of hot flushes in women with previous breast cancer.

Methods

A literature search was conducted in the databases of Medline, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), PSYCHINFO, AMED (Allied and Complementary Medicine), NCCAM (The National Centre for Complementary and Alternative Medicine).

Results

Black cohosh and phytoestrogens have received the most research attention but there is currently insufficient evidence to recommend either for relief of flushes. Black cohosh use appears safe in women with previous breast cancer. Opposing advice has been given regarding the safety of dietary phytoestrogen use for women with previous breast cancer, but there is emerging data that soyfood phytoestrogen intake may have a beneficial effect on tumour recurrence.

Conclusions

The majority of studies, regarding the efficacy of herbal treatments for hot flushes, have not been conducted in women with breast cancer and many are of short duration. Increased pharmacovigilance practices for herbal medicines are required with initiatives to stimulate reporting of suspected adverse reactions.     

Testosterone improves verbal learning and memory in postmenopausal women: Results from a pilot study

Objective

To explore the effects of testosterone on cognitive performance in healthy postmenopausal women.

Study design

Open-label pilot study. Nine postmenopausal women on non-oral hormone replacement therapy, aged 47–60 years received transdermal testosterone spray for 26 weeks. A control group of 30 women provided normative data for comparison.

Main outcome measures

Scores from a computerized cognitive test battery performed pre- and post treatment, at 0 and 26 weeks.

Results

There were no differences between treatment/normative groups in any parameter at baseline. At week 26 scores for the International Shopping list task including delayed recall (verbal learning and memory) and the continuous paired associate learning task (visual learning and memory) were significantly higher in the treatment group as compared to the normative group (p < 0.05). Significant improvements from baseline were observed for the International Shopping list delayed recall (verbal learning and memory) and Groton Maze recall tasks (visual learning and memory) for the treatment group (both p < 0.05), after 26 weeks. There were no significant differences between baseline and week 26 in the normative group. In the regression analysis which modeled the score at week 26, and which included a bootstrapping approach, the beta coefficient for the treatment group was statistically significant when age and baseline score were taken into account for the International Shopping list task including delayed recall (both p < 0.02).

Conclusion

Testosterone improved cognitive performance in the domain of verbal learning and memory in a pilot study of healthy postmenopausal women and is worthy of further exploration in a randomized placebo controlled study.     

An isopropanolic extract of black cohosh does not increase mammographic breast density or breast cell proliferation in postmenopausal women

OBJECTIVE: The aim of this study was to determine the effects of the isopropanolic extract of black cohosh (Remifemin) on mammographic breast density and breast epithelial proliferation in healthy, naturally postmenopausal women with climacteric symptoms. DESIGN: This was a prospective, open, uncontrolled drug safety study in which baseline status was compared with status after 6 months of treatment by blinded observers. A total of 74 women were treated with 40 mg black cohosh daily, and 65 women completed the study. Mammograms were performed, and breast cells were collected by percutaneous fine needle aspiration biopsies at baseline and after 6 months. Mammographic density was quantified according to the Wolfe classification or a percentage scale. Breast cell proliferation was assessed using the Ki-67/MIB-1 monoclonal antibody. Safety was monitored by adverse event reporting, laboratory assessments, and measurement of the endometrium by vaginal ultrasound. RESULTS: None of the women showed any increase in mammographic breast density. Furthermore, there was no increase in breast cell proliferation. The mean change +/- SD in proportion of Ki-67-positive cells was -0.5% +/- 2.4% (median, 0.0; 95% CI = -1.32 to 0.34) for paired samples. The mean change in endometrial thickness +/- SD was 0.0 +/- 0.9 mm (median, 0.0). A modest number of adverse events were possibly related to treatment, but none of these were serious. Laboratory findings and vital signs were normal. CONCLUSIONS: The findings suggest that the isopropanolic extract of black cohosh does not cause adverse effects on breast tissue. Furthermore, our data do not indicate to any endometrial or general safety concerns during 6 months of treatment.     

Effects of tibolone and combined 17beta-estradiol and norethisterone acetate on serum C-reactive protein in healthy post-menopausal women: a randomized trial

BACKGROUND: Serum C-reactive protein (CRP) is an independent risk factor for the development of cardiovascular diseases in healthy post-menopausal women. Oral unopposed and progestin-combined 17beta-estradiol (E(2)) increase serum CRP in post-menopausal women. The aim of this study was to compare the effects of tibolone, a steroid with estrogenic, androgenic or progestogenic properties, with a combination of E(2) and norethisterone acetate (E(2) + NETA) on serum CRP levels in healthy post-menopausal women. METHODS: A total of 139 post-menopausal women (mean age: 55 years, range 44-48) was randomly assigned to receive tibolone 1.25 mg/day (n = 52), tibolone 2.5 mg/day (n = 39) or E(2) 2 mg/day plus NETA 1 mg/day (n = 48) for 2 years. Serum CRP was measured at baseline and at 6, 12 and 24 months. RESULTS: Both doses of tibolone and E(2) + NETA increased serum CRP by a similar extent as soon as 6 months with a sustained effect over the 24 month treatment period. For example, after 6 months of treatment, serum CRP increased by a median of +106% (P < 0.001), +89% (P < 0.05) and +139% (P < 0.001) for tibolone 1.25 mg/day, tibolone 2.5 mg/day and E(2) + NETA respectively. CONCLUSIONS: Tibolone and E(2) + NETA significantly increase serum CRP levels in healthy post-menopausal women to a comparable extent. Relationships between induced elevated CRP levels with tibolone and E(2) + NETA and cardiovascular events require further studies.     

Postmenopausal hormone therapy and mammographic breast density

OBJECTIVE: The aim of this study was to evaluate the effects of different types of hormone replacement therapy (HRT) on mammographic density. MATERIALS AND METHODS: In a prospective 1-year study, 103 postmenopausal women were randomized to receive tibolone 2.5 mg/die, continuous conjugated equine estrogens 0.625 mg/die plus medroxyprogesterone acetate (MPA) 5mg/die or placebo. Mammograms were performed at baseline and after 12 months of treatment. Mammographic density was quantified according to the Wolfe classification. RESULTS: After 12 months of HRT 16 of the 35 patients (45.1%) receiving continuous combined hormonal therapy showed an increase of breast density change in the Wolfe classification. After treatment with tibolone, an up grading in breast density, according to Wolfe's classification, was found in 2 of the 43 patients (2.3%). No changes were recorded in the 25 patients of the control group. The difference between the group treated with continuous combined hormonal therapy and the control group was highly significant (p<0.001). The difference in breast density between patients in treatment with tibolone and the control group was not statistically significant (p=0.34). DISCUSSION: Continuous combination HRT may be more commonly associated with an increase of mammography density than tibolone treatment.     

Prospective evaluation of bone mineral density among middle-aged HIV-infected and uninfected women: Association between methadone use and bone loss

Objective

We undertook a prospective study to assess the impact of HIV infection on BMD in a cohort of HIV-infected and uninfected women that included illicit drug users, and to measure the contribution of traditional risk factors as well as HIV-related factors to loss of BMD over time.

Methods

We analyzed BMD at baseline and after ≥18 months in 245 middle-aged HIV-infected and 219 uninfected women, and conducted linear regression analysis to determine factors associated with annual BMD change at the femoral neck, total hip and lumbar spine.

Results

HIV-infected women had lower baseline BMD at the femoral neck and total hip compared with controls; unadjusted rates of BMD change did not differ by HIV status at any site. In multivariable analyses, we found that HIV seropositivity without protease inhibitor (PI) use was associated with BMD decline at the lumbar spine (−.009 g/cm² per year, p = .03). Additional factors associated with BMD decline were: postmenopausal status, lower BMI, and methadone use at the lumbar spine; postmenopausal status and hepatitis C seropositivity at the femoral neck; and postmenopausal status, age, smoking, and lower BMI at the total hip (all p < .05). Among HIV-infected women, ≥3 years of PI use was associated with an increase in lumbar spine BMD (.013 g/cm² per year, p = .008).

Conclusions

Bone loss among HIV-infected middle-aged women was modest, and possibly mitigated by PI use. Methadone use was associated with BMD decline, and should be considered when evaluating women for osteoporosis risk.     

Efficacy and tolerability of estradiol 1 mg and drospirenone 2 mg in postmenopausal Korean women: a double-blind, randomized, placebo-controlled, multicenter study

Objectives

The aim of this study was to demonstrate that the therapeutic efficacy of an estradiol 1 mg/drospirenone 2 mg (E2/DRSP) preparation is superior to a placebo in postmenopausal Korean women with hot flushes and other climacteric symptoms, and to demonstrate that this treatment is both safe and tolerable.

Methods

This was a double-blind, randomized, placebo-controlled, multicenter study over four 28-day treatment cycles. A total of 158 subjects were screened and 90 women were randomized into two treatment groups (E2/DRSP group, n = 45; placebo group, n = 45). The primary efficacy parameter was the individual relative change of hot flushes. The secondary efficacy parameters such as other climacteric, urogenital symptoms and vaginal bleeding patterns were also evaluated, and the occurrence of any adverse events was noted. In addition, physical, gynecological examinations and laboratory analyses were performed at the beginning and end of the study.

Results

The mean number of hot flushes per week during treatment weeks 3–16 decreased by 48.1% during treatment with placebo, and by 84.4% during treatment with E2/DRSP (p < 0.001). The E2/DRSP combination also reduced the incidence and intensity of menopausal symptoms in postmenopausal women. Most of adverse events was mild or moderate degree of intensity. None of the parameters measured in the study, including laboratory analyses, physical and gynecological examinations, vital signs, and weight, led to any concerns of safety.

Conclusions

The E2 1 mg/DRSP 2 mg combination tested in the study was efficacious and safe in the treatment of hot flushes and other climacteric symptoms in postmenopausal Korean women.     

The effect of low dose hormone therapy on mammographic breast density

OBJECTIVES: To evaluate the effect of two standard and one low dose continuous hormone therapy regimens on mammography. METHODS: One hundred and thirty-two non-hysterectomized postmenopausal women were randomly allocated either to conjugated equine estrogens 0.625 mg plus medroxyprogesterone acetate 5 mg (CEE/MPA, n=38), 17beta-estradiol 2 mg plus norethisterone acetate 1 mg (E2/NETA, n=44) or 17beta-estradiol 1 mg plus norethisterone acetate 0.5 mg (low E2/NETA, n=50). Treatment was continuous and the study period lasted 12 months. Main outcome measures were the changes according to Wolfe classification between baseline and 12-month mammograms. RESULTS: Five (13.2%) women in the CEE/MPA group showed an increase in breast density. Fourteen (31.8%) women on E2/NETA and 6 (12.2%) on low E2/NETA treatment revealed an increase in breast density. No woman exhibited an involution of fibroglandular tissue. CONCLUSIONS: Different hormone therapy regimens have a variable impact on breast density probably depending on the steroid used. Low dose hormone therapy associates with significantly lesser increase in breast density.     

Serum levels of ischemia modified albumin in overweight/obese postmenopausal women: a potential biomarker of atherosclerotic burden associated with oxidative stress

Objective

Menopause is associated with weight gain and an increase of cardiovascular risk. The aim of the present study was to estimate serum ischemia-modified albumin (IMA) levels in postmenopausal women and evaluate their association with body mass index (BMI) and coronary artery disease (CAD).

Methods

The study included 130 non-smoker postmenopausal women aged 43–80: 40 with BMI 26–32 kg/m² (Group A), 60 with BMI 21–25 kg/m² (Group B), and 30 with documented CAD and BMI 23–29 kg/m² (Group C). Serum IMA, albumin, hsCRP and NT-proBNP, glucose and insulin were measured. Homeostasis assessment model score (HOMA) and Quantitative insulin sensitivity index (QUICKI) were co-estimated.

Results

Serum IMA and IMA to albumin ratio were significantly elevated in Group A as compared to Group B (p < 0.001) and similar to those of Group C. hsCRP and NT-proBNP did not differ between Groups A and B while they were lower in comparison to Group C (p < 0.001). Glucose, insulin and HOMA were elevated in Group A compared to Group B (p < 0.001) while QUICKI was lower (p < 0.001). In Group A, IMA was positively correlated with BMI, hsCRP, insulin, HOMA and negatively with QUICKI. In postmenopausal women, multivariable regression analysis revealed that obesity was the strongest significant determinant of circulating IMA levels (p < 0.001) contributing, therefore, to the elevated serum IMA concentration.

Conclusions

Postmenopausal obesity is associated with elevated serum IMA possibly due to obesity associated oxidative stress. IMA measurement could provide an assessment of atherosclerotic burden in postmenopausal women. Further clinical evaluation is under investigation.     

Mammographic breast density changes after 1 year of tibolone use

Hormone replacement therapy (HRT) is widely used with a large variety of regimens and medications. For each of these regimens the goal is the same but there is always a fear about side effects, especially on breast. Mammographic screening is a standard tool for all women receiving hormone replacement therapy. Breast density is very important, because it interferes with the sensitivity of the evaluation and it is also a predictor of malignity. OBJECTIVE: We planned a study to investigate the effects of tibolone on mammographic breast density. DESIGN AND METHODS: We studied 70 postmenopausal women who started tibolone therapy (2.5 mg per day) after initial mammography and blood samples taken for biochemical examinations. None of the women used any hormone replacement therapy before. Eleven of them either discontinued the therapy or lost contact. After 1 year, we evaluated 59 women by mammographic status, using Wolfe classification. Mammographies were analyzed by two independent radiologists. RESULTS: Mammographies of 59 women were compared with the initial ones. While in the low density patterns, there was a slight increase (15%; P < 0.05); in the higher density groups, there was a decrease of 25% as observed by one radiologist, and 16% according to the other (P < 0.05). None of the women had a diffuse, high density pattern. There was no statistically significant inter-observer variation between two radiologists (P < 0.05). CONCLUSIONS: Wolfe classification allows easy interpretation of mammographic evaluation and the results are reproducible. Tibolone, as a tissue-specific steroid, does not have an estrogenic effect on breast cells. We found that it might limit, even reverse breast density increase, especially in postmenopausal women with high breast density.     

Postmenopausal hormone therapy before and after breast cancer: clinical experiences

Conventional oestrogen-based hormone therapy (HT) increases the incidence of breast pain and tenderness, mammographic density and the risk of breast cancer. Combined oestrogen plus progestogen therapy (EPT) increases the risk of breast cancer to a greater degree than oestrogen alone (ET). Attention must therefore be focused on identifying women at risk of breast cancer or on producing a HT that has fewer breast side effects. Randomised controlled trials have shown that while EPT induces breast tenderness or pain in up to 50% of women and increases mammographic density in up to 70% during the first year of treatment, only about as many as one-tenth women report breast tenderness or pain with tibolone and increases in mammographic density are rare, occurring with a similar incidence as seen in untreated controls. Many women with breast cancer suffer vasomotor symptoms rather than risk recurrence with conventional HT. However, in a small randomised controlled trial in women with early breast cancer undergoing adjuvant tamoxifen treatment, tibolone reduced hot flushes, night sweats and improved quality of life compared with placebo.     

Effects of tibolone and conventional HRT on the expression of estrogen and progesterone receptors in the breast

Objective

There is evidence that long-term hormone replacement therapy (HRT) is associated with an increased breast cancer risk. The aim of this study was to assess the effects of tibolone on estrogen and progesterone receptors in comparison to the effects of conventional HRT in the breast of surgically postmenopausal macaques.

Method

Sixty macaques were bilaterally ovariectomized 3 months before hormonal treatment was initiated. The animals were randomized into four treatment groups, including tibolone (TIB), conjugated equine estrogens (CEE), conjugated equine estrogens + medroxyprogesterone acetate (CEE + MPA) and control animals (C). After 2 years treatment, breast tissues were collected, fixed and paraffin embedded. Immunohistochemistry assays with monoclonal antibodies for estrogen receptors (ERα and ERβ) and progesterone receptors (PRA and PRB) were performed.

Results

The expression of ERα was markedly decreased in the CEE + MPA group as compared to C and TIB groups. The TIB group was not different from the C and CEE groups. No significant differences were found for ERβ immunostaining. The expression of PRA was strongly increased in the TIB group as compared to the C and CEE + MPA groups. Immunostaining of PRB was increased in the CEE and TIB treated animals as compared to both C and CEE + MPA groups.

Conclusions

Tibolone increased the expression of both PRA and PRB, without affecting ERα and ERβ expression in the macaque breast. These findings indicate that the effects of tibolone in breast tissue could be mediated via differential regulation of PRA and PRB isoforms and therefore distinct from those observed with conventional HRT.