To the Editor: In the discussion of biologic differences between male and female fertility (April 6 issue),1 Federman states that women are fertile for only 12 hours each month. Although the egg is viable for 12 hours or less, the window of fertility in women is approximately five to six days in each menstrual cycle,24 depending on the presence of estrogenic cervical mucus that maximizes the storage, survival, and transport of sperm until ovulation.4,5 Dr. Federman replies: Stanford rightly calls attention to the elegant estrogen-dominated events that precede ovulation and that favor passage of sperm through the cervix . . .
The fertile period of the human menstrual cycle consists of those days on which sexual intercourse can result in a pregnancy. Its duration is determined by the functional life span of the gametes within the female reproductive tract. Various mechanisms control gamete transport and survival in the reproductive tract of the human female. The ovarian hormones estradiol and progesterone have an important role in regulating these mechanisms. The nature of cervical mucus and its governing influences on sperm transport and survival following coitus are of prime importance in defining the fertile days of the menstrual cycle. Man's early concepts of the fertile period were often based on erroneous theories of the female reproductive cycle. It is only since the late 1920's that a true understanding of ovulation and the menstrual cycle has evolved. Current approaches in natural family planning to recognizing the fertile and infertile days of the menstrual cycle are discussed and evaluated.
Lincoff AM et al., 2023·The New England journal of medicine
The cardiovascular safety of testosterone-replacement therapy in middle-aged and older men with hypogonadism has not been determined. In a multicenter, randomized, double-blind, placebo-controlled, noninferiority trial, we enrolled 5246 men 45 to 80 years of age who had preexisting or a high risk of cardiovascular disease and who reported symptoms of hypogonadism and had two fasting testosterone levels of less than 300 ng per deciliter. Patients were randomly assigned to receive daily transdermal 1.62% testosterone gel (dose adjusted to maintain testosterone levels between 350 and 750 ng per deciliter) or placebo gel. The primary cardiovascular safety end point was the first occurrence of any component of a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, assessed in a time-to-event analysis. A secondary cardiovascular end point was the first occurrence of any component of the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization, assessed in a time-to-event analysis. Noninferiority required an upper limit of less than 1.5 for the 95% confidence interval of the hazard ratio among patients receiving at least one dose of testosterone or placebo. The mean (±SD) duration of treatment was 21.7±14.1 months, and the mean follow-up was 33.0±12.1 months. A primary cardiovascular end-point event occurred in 182 patients (7.0%) in the testosterone group and in 190 patients (7.3%) in the placebo group (hazard ratio, 0.96; 95% confidence interval, 0.78 to 1.17; P<0.001 for noninferiority). Similar findings were observed in sensitivity analyses in which data on events were censored at various times after discontinuation of testosterone or placebo. The incidence of secondary end-point events or of each of the events of the composite primary cardiovascular end point appeared to be similar in the two groups. A higher incidence of atrial fibrillation, of acute kidney injury, and of pulmonary embolism was observed in the testosterone group. In men with hypogonadism and preexisting or a high risk of cardiovascular disease, testosterone-replacement therapy was noninferior to placebo with respect to the incidence of major adverse cardiac events. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).