RESUMEN

Lung cancer incidence and mortality have significantly increased in women worldwide. Lung adenocarcinoma is the most common form of lung cancer globally. This type of lung cancer shows differences by sex, including the mutational burden, behavior, clinical characteristics, and response to treatment. The effect of sex on lung cancer patients' survival is still controversial; however, lung adenocarcinoma is considered a different disease in women and men. Moreover, lung adenocarcinoma is strongly influenced by estrogen and is also different depending on the hormonal status of the patient. Young pre-menopausal women have been explored as an independent group. They presented in more advanced stages at diagnosis, exhibited more aggressive tumors, and showed poor survival compared to men and post-menopausal women, supporting the role of sex hormones in this pathology. Several reports indicate the estrogen's role in lung carcinogenesis and tumor progression. Thus, there are currently some clinical trials testing the efficacy of antihormonal therapy in lung cancer treatment. This mini review shows the updated data about lung cancer in women, its characteristics, the etiological factors that influence carcinogenesis, and the critical role of estrogen in lung cancer and treatment.

RESUMEN

Lung cancer (LC) is the leading cause of cancer death in men worldwide and has significantly increased in women. Differences in non-small cell lung cancer (NSCLC) behavior, prognosis, and response to treatment have been reported by sex and hormonal status, with premenopausal women presenting the worst prognosis compared to postmenopausal women and men. Additionally, the use of hormonal replacement therapy significantly increases NSCLC mortality; supporting the role of estrogen signaling in the pathogenesis of LC. The mechanisms by which estrogen promotes lung carcinogenesis have not been fully elucidated. Estrogen, through its receptor, can stimulate LC cell proliferation, death resistance, angiogenesis, migration and metastasis. Estrogen also induces expression of pro-inflammatory proteins and ligands that promote tumor evasion, suggesting that estrogen might modify the microenvironment and anti-tumor immune response. Recent reports have shown an interaction between the epidermal growth factor receptor (EGFR) pathway and estrogen signaling in lung adenocarcinoma, whence, combined treatment based on tyrosine kinase inhibitors (TKIs) and antiestrogen therapy is beginning to be evaluated. This review focuses on the differences in NSCLC behavior by sex and hormonal status, highlighting the role of estrogen and its receptors in lung carcinogenesis and LC prognosis. Due to the importance of estrogen in NSCLC development and progression we finally discuss the potential of antiestrogen therapy in LC treatment and show the results from preclinical and clinical trials.

RESUMEN

Chlormadinone acetate (CMA) is a progesterone derivative (17α-acetoxy-6-chloro-4,6-pregnadiene-3,20-dione), first synthesized in 1961. It was used as progestin-based hormone replacement therapy; since 1999 it was first used for oral contraception combined with ethinyl estradiol (EE). CMA exerts a potent progestagenic effect, about one third higher than that observed with endogenous progesterone. CMA is also an anti-estrogen, showing no androgenic effects (at birth control dose). Unlike progesterone, it has a mild glucosteroidal effect with no anti-mineralocorticoid effect at all. These biological actions have allowed CMA to have a role for therapeutic use in dysmenorrhea, hyperandrogenism, and as a contraceptive agent. In addition, CMA has exhibited beneficial neuroendocrine effects on women's mood. CMA-EE combination has shown excellent contraceptive efficacy, high tolerability, and compliance due to its risk-benefit profile, having additional benefits on skin and hair, such as reduction of seborrhea and acne. Metabolic tolerance of CMA has been demonstrated in several clinical studies. Currently, CMA is formulated to be taken as oral caplets in a 21 caplets package containing 0.03 mg/EE and 2 mg CMA per pill with/without seven placebo additional pills. Another presentation has 24 caplets containing 0.02 mg/EE and 2 mg CMA plus four placebo pills.

Asunto(s)

RESUMEN

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered.

Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente.

Asunto(s)

RESUMEN

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered. (AU)

Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente. (AU)

Asunto(s)

RESUMEN

The effects of prenatal exposure to clomiphene citrate in sexual behavior, organ weight and hormone concentrations of male and female rats was evaluated. The animals received four doses of clomiphene citrate 2 mg/mL each during the prenatal period (21 days of gestation DG21) on days 1 (DN1), 2 (DN2) and 3 (DN3) after the birth of the puppies. The treatment led to the development of polycystic ovaries in 70% of the females, masculinization of female sexual behavior and changes in sexual behavior of males evidenced by the reduction in the number of ejaculations. In regards to hormone levels, a decrease in the FSH levels in male offspring was observed. It was concluded that clomiphene citrate interferes with the reproductive capacity of male and female rats and female sexual orientation when prenatally administered.

Foram investigados os efeitos da exposição perinatal ao citrato de clomifeno no comportamento sexual, peso dos órgãos e concentração hormonal de ratos machos e fêmeas. Os animais receberam quatro doses de 2 mg/mL de citrato de clomifeno, no período perinatal (21 dias de gestação DG21), nos dias 1 (DN1), 2 (DN2) e 3 (DN3) após o nascimento dos filhotes. O tratamento causou desenvolvimento de ovário policístico em 70% das fêmeas, masculinização do comportamento sexual das fêmeas e alteração do comportamento sexual dos machos evidenciado pela redução no número de ejaculações. Em relação aos níveis hormonais, observou-se diminuição de FSH na prole masculina. Concluiu-se que o citrato de clomifeno interfere na capacidade reprodutiva de ratos machos e fêmeas, e na orientação sexual de fêmeas, quando administrado perinatalmente.