Catégorie : Chiffres et études

Michels KA, Pfeiffer RM, Brinton LA, Trabert B. Modification of the Associations Between Duration of Oral Contraceptive Use and Ovarian, Endometrial, Breast, and Colorectal Cancers. JAMA Oncol. Published online January 18, 2018. doi:10.1001/jamaoncol.2017.4942

Source :Journal of the American Medical Association

Charlotte Wessel Skovlund, Ph.D., Lina Steinrud Mørch, Ph.D., Lars Vedel Kessing, D.M.Sc., Theis Lange, Ph.D., Øjvind Lidegaard, D.M.Sc.
Received: June 06, 2017
Accepted: August 24, 2017
Published online: November 17, 2017 | https://doi.org/10.1176/appi.ajp.2017.17060616
Source: The American Journal of Psychiatry

Abstract
Objective:
The purpose of this study was to assess the relative risk of suicide attempt and suicide in users of hormonal contraception.

Method:
The authors assessed associations between hormonal contraceptive use and suicide attempt and suicide in a nationwide prospective cohort study of all women in Denmark who had no psychiatric diagnoses, antidepressant use, or hormonal contraceptive use before age 15 and who turned 15 during the study period, which extended from 1996 through 2013. Nationwide registers provided individually updated information about use of hormonal contraception, suicide attempt, suicide, and potential confounding variables. Psychiatric diagnoses or antidepressant use during the study period were considered potential mediators between hormonal contraceptive use and risk of suicide attempt. Adjusted hazard ratios for suicide attempt and suicide were estimated for users of hormonal contraception as compared with those who never used hormonal contraception.

Results:
Among nearly half a million women followed on average for 8.3 years (3.9 million person-years) with a mean age of 21 years, 6,999 first suicide attempts and 71 suicides were identified. Compared with women who never used hormonal contraceptives, the relative risk among current and recent users was 1.97 (95% CI=1.85–2.10) for suicide attempt and 3.08 (95% CI=1.34–7.08) for suicide. Risk estimates for suicide attempt were 1.91 (95% CI=1.79–2.03) for oral combined products, 2.29 (95% CI=1.77–2.95) for oral progestin-only products, 2.58 (95% CI=2.06–3.22) for vaginal ring, and 3.28 (95% CI=2.08–5.16) for patch. The association between hormonal contraceptive use and a first suicide attempt peaked after 2 months of use.

Conclusions:
Use of hormonal contraception was positively associated with subsequent suicide attempt and suicide. Adolescent women experienced the highest relative risk.

Lina S. Mørch, Ph.D., Charlotte W. Skovlund, M.Sc., Philip C. Hannaford, M.D., Lisa Iversen, Ph.D., Shona Fielding, Ph.D., and Øjvind Lidegaard, D.M.Sci.

N Engl J Med 2017; 377:2228-2239December 7, 2017DOI: 10.1056/NEJMoa1700732

Source: The New England Journal of Medecine

Background

Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer.

Methods

We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders.

Results

Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen–progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year.

Conclusions

The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.)

Source:Proceedings of National Academy of Sciences (PNAS)

Edited by David E. Clapham, Howard Hughes Medical Institute, Boston Children’s Hospital, Boston, MA, and approved April 20, 2017 (received for review January 10, 2017)

Significance

The calcium channel of sperm—CatSper—is vital for male fertility. CatSper is activated by the hormone progesterone, but its pharmacological profile is not well studied. By exploring steroid selectivity of CatSper activation, we found one additional agonist—pregnenolone sulfate—and the two plant-derived inhibitors pristimerin and lupeol. By averting sperm hyperactivation, both inhibitors can prevent fertilization, thus acting as contraceptive agents. Additionally, by exploring CatSper regulation by endogenous steroids, we explain why CatSper is silent within the male reproductive tract and is only activated in close proximity to the egg. Interestingly, both testosterone and hydrocortisone antagonize the action of progesterone at physiological concentrations, which may explain why elevated levels of these steroids in the female organism affect fertility.

Abstract
The calcium channel of sperm (CatSper) is essential for sperm hyperactivated motility and fertility. The steroid hormone progesterone activates CatSper of human sperm via binding to the serine hydrolase ABHD2. However, steroid specificity of ABHD2 has not been evaluated. Here, we explored whether steroid hormones to which human spermatozoa are exposed in the male and female genital tract influence CatSper activation via modulation of ABHD2. The results show that testosterone, estrogen, and hydrocortisone did not alter basal CatSper currents, whereas the neurosteroid pregnenolone sulfate exerted similar effects as progesterone, likely binding to the same site. However, physiological concentrations of testosterone and hydrocortisone inhibited CatSper activation by progesterone. Additionally, testosterone antagonized the effect of pregnenolone sulfate. We have also explored whether steroid-like molecules, such as the plant triterpenoids pristimerin and lupeol, affect sperm fertility. Interestingly, both compounds competed with progesterone and pregnenolone sulfate and significantly reduced CatSper activation by either steroid. Furthermore, pristimerin and lupeol considerably diminished hyperactivation of capacitated spermatozoa. These results indicate that (i) pregnenolone sulfate together with progesterone are the main steroids that activate CatSper and (ii) pristimerin and lupeol can act as contraceptive compounds by averting sperm hyperactivation, thus preventing fertilization.

Abigail R A Aiken, Irena Digol, James Trussell,Rebecca Gomperts

BMJ 2017; 357 doi: https://doi.org/10.1136/bmj.j2011 (Published 16 May 2017)
Cite this as: BMJ 2017;357:j2011

Source: BMJ