Hormone replacement therapy in cancer survivors: Utopia?

As growing of old women population, menopausal women will also increase: an accurate estimation of postmenopausal population is an essential information for health care providers considering that with aging, the incidence of all cancers is expected to increase. Hormone replacement therapy (HRT) has proven to be highly effective in alleviating menopausal symptoms such as hot flashes, night sweats, dyspareunia, sexual disorders, and insomnia and in preventing osteoporosis. According to preclinical data, estrogen and progesterone are supposed to be involved in the induction and progression of breast and endometrial cancers. Similarly, in epithelial ovarian cancer (EOC), the pathogenesis seems to be at least partly hormonally influenced. Is HRT in gynecological cancer survivors possible? The literature data are controversial. Many clinicians remain reluctant to prescribe HRT for these patients due to the fear of relapse and the risk to develop coronary heart disease or breast cancer. Before the decision to use HRT an accurate counselling should be mandatory in order to individualizing on the basis of potential risks and benefits, including a close follow-up. Nevertheless, we do believe that with strong informed consent doctors may individually consider to prescribe some course of HRT in order to minimize menopausal symptoms and disease related to hormonal reduction.

Role of paroxetine in the management of hot flashes in gynecological cancer survivors: Results of the first randomized single-center controlled trial.

OBJECTIVES: To examine the effects of paroxetine supplementation on hot flashes and sleep in gynecological cancer survivors. METHODS: In a randomized, double-blind, placebo-controlled study, postmenopausal women with a prior history of stage 0-III gynecological cancer who had completed active cancer treatment (including hormonal therapy) were randomly assigned 1:1 to either 7.5mg oral paroxetine or placebo daily for 16weeks. Sleep and hot flashes were assessed at baseline, week 4 and week 16. RESULTS: Eighty women (91%) completed the study. We found out a statistically significant difference in weekly reductions in VMS frequency and severity for paroxetine 7.5mg than for placebo on week 4 and 16. Regarding sleep characteristics, the analysis of data through week 16 reported a statistically significant reduction in the number of nighttime awakenings attributed to VMS among participants receiving paroxetine than among participants receiving placebo on baseline and weeks. The duration of sleep per night increased significantly more among participants receiving paroxetine than among those receiving placebo at all post baseline time points. No significant differences in sleep-onset latency were noted between the two treatment arms during the course of the study. Paroxetine was well-tolerated with a high level of compliance. In our cohort of patients, no serious adverse events have been reported. CONCLUSIONS: This is the first randomized placebo-controlled study in gynecological cancer survivors that demonstrates that paroxetine significantly reduces hot flashes in weekly frequency and severity and the number of nighttime awakenings attributed to vasomotor symptoms, increasing sleep duration.

Positive effects on cardiovascular and breast metabolic markers of oral estradiol and dydrogesterone in comparison with transdermal estradiol and norethisterone acetate.

OBJECTIVES: To assess differences in two sequential combined hormone replacement therapy (HRT) products on selected cardiovascular and breast metabolic markers. The products were different concerning the route of administration of estradiol and its combined progestin, either oral or transdermal, and the androgenic properties of progestogens, respectively, dydrogesterone and norethisterone acetate. METHODS: One hundred and nineteen healthy non-hysterectomized postmenopausal women were included in this open, multi-center, two parallel group trial. They were randomized to a treatment of six 28-day cycles with oral estradiol sequentially combined with dydrogesterone (oE2/D10) or a sequential combination patch of estradiol plus norethisterone acetate (tdE/NETA). At baseline and after six cycles the high-density lipoprotein cholesterol (HDL-C), the sex hormone binding globulin (SHBG) and the total insulin-like growth factor-I (IGF-I) blood levels were determined by a central laboratory. A total of 89 women were compliant to the protocol. RESULTS: After six cycles, a statistically significant difference (P<0.001) concerning HDL-C, SHBG and IGF-I levels was found between the two treatment groups. The HDL-C levels were increased in the oE2/D10 group and decreased in the tdE/NETA group, with a final difference of about 0.3 mmol/l. The oE2/D10 treatment induced a sharp increase (about 57 mmol/l) in SHBG levels. IGF-I levels decreased with both the products, but the difference in favor of the oE2/D10 treatment was of about 30 ng/ml. Moreover, patients on tdE/NETA with an IGF-I baseline value below the median showed an increase. CONCLUSION: Oral estradiol sequentially combined with dydrogesterone, a non-androgenic progestogen, induced positive changes of some cardiovascular (HDL-C) and breast (SHBG and IGF-I) metabolic markers. These effects were significantly different from those obtained with a transdermal estradiol associated to an androgenic progestogen.