What do we know and what don't we know about tamoxifen in the human uterus

Friedl, Andreas; Jordan, V. Craig

doi:10.1007/bf00689674

Cited by 42 publications

(13 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Women receiving long-term treatment with tamoxifen have shown an increase in the incidence of endometrial hyperplasia, including carcinoma (14,33,34). Moreover, an association has been found between the development of endometrial lesions and the duration of treatment as well as the dose of tamoxifen administered (35-37).…”

Section: Discussionmentioning

confidence: 99%

Morphological Changes Induced by 6-Month Treatment of Intact and Ovariectomized Mice with Tamoxifen and the Pure Antiestrogen EM-800

Sourla¹,

Luo²,

Labrie³

et al. 1997

Endocrinology

View full text Add to dashboard Cite

The present study compares the effects of tamoxifen and EM-800, both administered at the oral daily dose of 100 g for 6 months, on the uterus, vagina, and mammary gland in the mouse at histopathological examination. Treatment of intact animals with EM-800 resulted in uterine and vaginal atrophy even greater than that achieved after ovariectomy, while the developmental growth of the mammary gland was completely blocked and serum LH was increased. In ovariectomized animals, treatment with EM-800 decreased uterine and vaginal wt below the values observed in control ovariectomized mice while no significant change was observed on serum LH, thus indicating the lack of estrogenic activity of EM-800.Tamoxifen, on the other hand, showed a stimulatory estrogeniclike action on the mouse uterus in both intact and ovariectomized animals, thus resulting in moderate to severe endometrial hyperplasia. These morphological changes were accompanied by a marked stimulation of both the estrogenic and androgenic 17␤-hydroxysteroid dehydrogenase as well as 5␣-reductase uterine activities. The histological atrophic changes observed in the vagina after tamoxifen treatment were less pronounced than those seen after treatment with EM-800. The agonistic estrogen-like action of tamoxifen was also illustrated by the suppression of serum LH levels in ovariectomized animals.A marked stimulation of the ovarian stroma, accompanied by a significant reduction in folliculogenic activity, was observed after EM-800 or tamoxifen administration, although the interstitial ovarian hyperplasia was more pronounced after EM-800 treatment. While both antiestrogens blocked the developmental growth of the mammary gland, EM-800 showed more potent antiestrogenic activity than tamoxifen. The highly potent and specific antiestrogenic activity of EM-800 suggests that this compound could improve the therapy of breast cancer while avoiding the undesirable stimulation of the endometrium. (Endocrinology 138: [5605][5606][5607][5608][5609][5610][5611][5612][5613][5614][5615][5616][5617] 1997)

show abstract

Section: Discussionmentioning

confidence: 99%

Morphological Changes Induced by 6-Month Treatment of Intact and Ovariectomized Mice with Tamoxifen and the Pure Antiestrogen EM-800

Sourla¹,

Luo²,

Labrie³

et al. 1997

Endocrinology

View full text Add to dashboard Cite

show abstract

“…Considering the major concern related to the stimulatory effect of estrogens on endometrial proliferation with the related risk of endometrial carcinoma [77, 78], an endometrial biopsy was performed before starting treatment and after 12 months of DHEA administration. As can be seen in fig.…”

Section: Predominant Estrogenic Effect Of Dhea In the Vagina And No Ementioning

confidence: 99%

Intracrinology and The Skin

et al. 2000

View full text Add to dashboard Cite

The skin, the largest organ in the human body, is composed of a series of androgen-sensitive components that all express the steroidogenic enzymes required to transform dehydroepiandrosterone (DHEA) into dihydrotestosterone (DHT). In fact, in post-menopausal women, all sex steroids made in the skin are from adrenal steroid precursors, especially DHEA. Secretion of this precursor steroid by the adrenals decreases progressively from the age of 30 years to less than 50% of its maximal value at the age of 60 years. DHEA applied topically or by the oral route stimulates sebaceous gland activity, the changes observed being completely blocked in the rat by a pure antiandrogen while a pure antiestrogen has no significant effect, thus indicating a predominant or almost exclusive androgenic effect. In human skin, the enzyme that transforms DHEA into androstenedione is type 1 3β-hydroxysteroid dehydrogenase (type 1 3β-HSD) as revealed by RNase protection and immunocytochemistry. The conversion of androstenedione into testosterone is then catalyzed in the human skin by type 5 17β-HSD. All the epidermal cells and cells of the sebaceous glands are labelled by type 5 17β-HSD. This enzyme is also present at a high level in the hair follicles. Type 1 is the 5α-reductase isoform responsible in human skin for the conversion of testosterone into DHT. In the vagina, on the other hand, DHEA exerts mainly an estrogenic effect, this effect having been demonstrated in the rat as well as in post-menopausal women. On the other hand, in experimental animals as well as in post-menopausal women, DHEA, at physiological doses, does not affect the endometrial epithelium, thus indicating the absence of DHEA-converting enzymes in this tissue, and avoiding the need for progestins when DHEA is used as hormone replacement therapy.

show abstract

“…In the uterus, and especially in the endometrium, the effect of antioestrogens resembles that of oestrogens (Lahti et al, 1993;Friedl and Jordan, 1994), and in this regard tamoxifen may be more potent than toremifene at least in animal experiments (DiSalle et al, 1990). The use of both tamoxifen and toremifene has been linked to the risk of endometrial polyps (Tomás et al, 1995;Barakat, 1996) and tamoxifen may increase the risk of endometrial cancer (Fisher et al, 1994;Rutqvist et al, 1995;Fisher et al, 1998;Early Breast Cancer Trialists Collaborative Group, 1998).…”

mentioning

confidence: 99%

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women

et al. 2001

View full text Add to dashboard Cite

To assess and compare the gynaecological consequences of the use of 2 antioestrogens we examined 167 postmenopausal breast cancer patients before and during the use of either tamoxifen (20 mg/day, n = 84) or toremifene (40 mg/day, n = 83) as an adjuvant treatment of stage II–III breast cancer. Detailed interview concerning menopausal symptoms, pelvic examination including transvaginal sonography (TVS) and collection of endometrial sample were performed at baseline and at 6, 12, 24 and 36 months of treatment. In a subgroup of 30 women (15 using tamoxifen and 15 toremifene) pulsatility index (PI) in an uterine artery was measured before and at 6 and 12 months of treatment. The mean (±SD) follow-up time was 2.3 ± 0.8 years. 35% of the patients complained of vasomotor symptoms before the start of the trial. This rate increased to 60.0% during the first year of the trial, being similar among patients using tamoxifen (57.1%) and toremifene (62.7%). Vaginal dryness, which was present in 6.0% at baseline, increased during the use of tamoxifen (26.2%) and toremifene (24.1%). Endometrial thickness increased from baseline (3.9 ± 2.7 mm) to 6.8 ± 4.2 mm at 6 months ( P < 0.001), and no difference emerged between the 2 regimens in this regard. Before the start of the antioestrogen regimen, the endometrium was atrophic in 71 (75.5%) and proliferative in 19 of 94 (20.2%) samples; 4 patients had benign endometrial polyps. During the use of antioestrogen altogether 339 endometrial samples were taken (159 in tamoxifen group, 180 in toremifene group). The endometrium was proliferative more often in the tamoxifen group (47.8%) than in the toremifene group (32.2%) ( P < 0.0001). 20 patients had a total of 24 polyps (17 in tamoxifen and 9 in toremifene group, P < 0.05) during the use of antioestrogens. One patient in the toremifene group developed endometrial adenocarcinoma at 12 months, and one patient had breast cancer metastasis on the endometrium. Tamoxifen failed to affect the PI in the uterine artery, but toremifene reduced it by 15.0% ( P < 0.05) by 12 months. In conclusion, tamoxifen and toremifene cause similarly vasomotor and vaginal symptoms. Neither regimen led to the development of premalignant endometrial changes. Our data suggest that so close endometrial surveillance as used in our study may not be mandatory during the first 3 years of use of antioestrogen treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com

show abstract

What do we know and what don't we know about tamoxifen in the human uterus

Cited by 42 publications

References 59 publications

Morphological Changes Induced by 6-Month Treatment of Intact and Ovariectomized Mice with Tamoxifen and the Pure Antiestrogen EM-800

Morphological Changes Induced by 6-Month Treatment of Intact and Ovariectomized Mice with Tamoxifen and the Pure Antiestrogen EM-800

Intracrinology and The Skin

Prospective study on gynaecological effects of two antioestrogens tamoxifen and toremifene in postmenopausal women

Contact Info

Product

Resources

About