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Tamoxifen-induced ovarian hyperstimulation during premenopausal hormonal therapy for breast cancer in Japanese women.

Yamazaki R, Inokuchi M, Ishikawa S, Myojo S, Iwadare J, Bono Y, Mizumoto Y, Nakamura M, Takakura M, Iizuka T, Ohta T, Fujiwara H - Springerplus (2015)

Bottom Line: There was no significant difference in age or FSH concentration between the two groups.These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment.Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641 Japan.

ABSTRACT

Purpose: Tamoxifen is an anti-estrogenic drug that is widely used for endocrine-dependent breast cancer as adjuvant hormonal therapy, and its use has been reported to be frequently associated with high levels of serum estradiol. Since the population of premenopausal women receiving tamoxifen therapy is growing in Japan, we retrospectively analyzed the incidence of ovarian hyperstimulation by tamoxifen therapy in Japanese women.

Methods: Eleven patients who received surgical therapy for endocrine-dependent breast cancer and showed high values of serum estradiol during post-operative tamoxifen therapy were recruited in this study and evaluated by examining the serum concentration of follicular stimulating hormone (FSH) and follicular development.

Results: The mean age, serum concentrations of estradiol and FSH, and follicular diameter were 41.3 years old, 1015.8 pg/mL, 11.8 mIU/mL, and 3.47 cm, respectively. In 6 cases, multiple follicular development was observed, while the other cases showed single follicular development with a mean serum estradiol level of 848.6 pg/mL and follicular diameter of 4.46 cm. There was no significant difference in age or FSH concentration between the two groups. The mean periods from the start of the single administration of tamoxifen to the initial detection of a high estradiol concentration was 716.5 days.

Conclusions: These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment. Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

No MeSH data available.


Related in: MedlinePlus

Inhibitory action of TAM on negative feedback to the hypothalamic-pituitary-axis by estrogen during the follicular phase. TAM can inhibit negative feedback to the hypothalamic-pituitary-axis by estrogen, leading to the increases of FSH and LH secretion by the pituitary gland and then inducing multiple follicular development
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Fig1: Inhibitory action of TAM on negative feedback to the hypothalamic-pituitary-axis by estrogen during the follicular phase. TAM can inhibit negative feedback to the hypothalamic-pituitary-axis by estrogen, leading to the increases of FSH and LH secretion by the pituitary gland and then inducing multiple follicular development

Mentions: The formation of a couple of ovarian follicular cysts was observed not only in three cases with regular menstruation, but also in the other three cases that had been clinically diagnosed as chemotherapy-induced menopause. This suggests that TAM can induce multiple follicular development, which is usually observed in ovulation induction using an anti-estrogenic agent, clomiphene (Nasseri and Ledger 2001). Anti-estrogenic drugs are considered to inhibit the hypothalamic-pituitary-axis by negative feedback to stimulate the secretion of pituitary gonadotropins such as FSH and luteinizing hormone (LH) (Fig. 1). Since the pulsatile secretion of pituitary gonadotropins is important in the selection and/or promotion of follicular development (Skorupskaite et al. 2014), more examinations including the rhythmic changes in pulsatile secretion by TAM are necessary to clarify the precise mechanisms.Fig. 1


Tamoxifen-induced ovarian hyperstimulation during premenopausal hormonal therapy for breast cancer in Japanese women.

Yamazaki R, Inokuchi M, Ishikawa S, Myojo S, Iwadare J, Bono Y, Mizumoto Y, Nakamura M, Takakura M, Iizuka T, Ohta T, Fujiwara H - Springerplus (2015)

Inhibitory action of TAM on negative feedback to the hypothalamic-pituitary-axis by estrogen during the follicular phase. TAM can inhibit negative feedback to the hypothalamic-pituitary-axis by estrogen, leading to the increases of FSH and LH secretion by the pituitary gland and then inducing multiple follicular development
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4539309&req=5

Fig1: Inhibitory action of TAM on negative feedback to the hypothalamic-pituitary-axis by estrogen during the follicular phase. TAM can inhibit negative feedback to the hypothalamic-pituitary-axis by estrogen, leading to the increases of FSH and LH secretion by the pituitary gland and then inducing multiple follicular development
Mentions: The formation of a couple of ovarian follicular cysts was observed not only in three cases with regular menstruation, but also in the other three cases that had been clinically diagnosed as chemotherapy-induced menopause. This suggests that TAM can induce multiple follicular development, which is usually observed in ovulation induction using an anti-estrogenic agent, clomiphene (Nasseri and Ledger 2001). Anti-estrogenic drugs are considered to inhibit the hypothalamic-pituitary-axis by negative feedback to stimulate the secretion of pituitary gonadotropins such as FSH and luteinizing hormone (LH) (Fig. 1). Since the pulsatile secretion of pituitary gonadotropins is important in the selection and/or promotion of follicular development (Skorupskaite et al. 2014), more examinations including the rhythmic changes in pulsatile secretion by TAM are necessary to clarify the precise mechanisms.Fig. 1

Bottom Line: There was no significant difference in age or FSH concentration between the two groups.These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment.Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920-8641 Japan.

ABSTRACT

Purpose: Tamoxifen is an anti-estrogenic drug that is widely used for endocrine-dependent breast cancer as adjuvant hormonal therapy, and its use has been reported to be frequently associated with high levels of serum estradiol. Since the population of premenopausal women receiving tamoxifen therapy is growing in Japan, we retrospectively analyzed the incidence of ovarian hyperstimulation by tamoxifen therapy in Japanese women.

Methods: Eleven patients who received surgical therapy for endocrine-dependent breast cancer and showed high values of serum estradiol during post-operative tamoxifen therapy were recruited in this study and evaluated by examining the serum concentration of follicular stimulating hormone (FSH) and follicular development.

Results: The mean age, serum concentrations of estradiol and FSH, and follicular diameter were 41.3 years old, 1015.8 pg/mL, 11.8 mIU/mL, and 3.47 cm, respectively. In 6 cases, multiple follicular development was observed, while the other cases showed single follicular development with a mean serum estradiol level of 848.6 pg/mL and follicular diameter of 4.46 cm. There was no significant difference in age or FSH concentration between the two groups. The mean periods from the start of the single administration of tamoxifen to the initial detection of a high estradiol concentration was 716.5 days.

Conclusions: These findings indicate that tamoxifen could stimulate the ovarian function even after 2-year treatment. Since single and multiple follicular developments with large sizes were observed, dual mechanisms through the inhibition of both negative and positive feedback to the hypothalamic-pituitary-axis can be proposed to explain the adverse effects of tamoxifen on ovarian function.

No MeSH data available.


Related in: MedlinePlus