Tamoxifen treatment and gynecologic side effects: a review.
OBJECTIVE
To review the literature on tamoxifen side effects on the female genital tract and psychosexual function in premenopausal and postmenopausal women.


METHODS
We used the English-language literature in MEDLINE and reference lists from selected articles. Search terms included: "tamoxifen and estrogen receptor," "transcription activation," "premenopause," "postmenopause," "vaginal epithelium," "uterus," "endometrial hyperplasia," "polyps," "endometrial cancer," "sonography," "sonohysterography," "hysteroscopy," "myometrium," "myoma," "sarcoma," "endometriosis," "ovarian cysts," "hot flushes," "concentration problems," "sleep disturbance," "vaginal dryness," "sexual function," "libido," "dyspareunia," and "quality of life." No study-type restrictions were imposed.


METHODS
With respect to clinical studies we included case cohort studies, observational studies; if no trials were available on a subject, case reports published in peer-reviewed journals were selected. For the discussion on endometrial surveillance of tamoxifen users, letters and editorials published in peer-reviewed journals also were used. Subjects of interest were mechanism of action of tamoxifen, tamoxifen and the vaginal epithelium, endometrium, mesenchymal tumors of the uterus, ovaries, sexual function, and vasomotor instability.


RESULTS
Eligible studies were analyzed to determine their usefulness in this review. Data from trials that evaluated tamoxifen side effects on specific genital tissues were combined, with special interest in differentiation of side effects in premenopausal and postmenopausal women. Weighted estimates of severity and extent of side effects were usually not possible because of lack of randomized trials. Only the risk of endometrial cancer in relation to tamoxifen treatment could be estimated.


CONCLUSIONS
The gynecologic side effects of tamoxifen are diverse and reflect the complexity of its mechanism of action, with agonistic and antagonistic effects on various tissues, depending on the ambient estradiol concentration and hence menopausal status of the patient. The most frequently reported side effect was hot flushes, and the most worrisome gynecologic side effect was a two- to three-fold increased risk of endometrial cancer in postmenopausal women. Despite its side effects, the benefits of tamoxifen in controlling breast cancer or prevention of its relapse are still without debate.
Mourits
M J
MJ
Department of Obstetrics and Gynecology, University Hospital Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands. m.j.e.mourits@og.azg.nl
De Vries
E G
EG
Willemse
P H
PH
Ten Hoor
K A
KA
Hollema
H
H
Van der Zee
A G
AG
D001943:Breast Neoplasms / Q000517:prevention & control*; D016889:Endometrial Neoplasms / Q000139:chemically induced*; D004965:Estrogen Antagonists / Q000009:adverse effects*; D005260:Female; D019584:Hot Flashes / Q000175:diagnosis; D006801:Humans; D008593:Menopause; D020018:Sexual Dysfunctions, Psychological / Q000139:chemically induced; D013629:Tamoxifen / Q000009:adverse effects*
D004965:Estrogen Antagonists; D013629:Tamoxifen