Conceptive delays of twin-prone mothers: a demographic epidemiologic approach

We studied the time interval to the first birth and to the twin birth using statistical and mathematical models in two groups of mothers, those with twins and those with singletons, from the same population. We made use of a pair-matched case-control design. We treated the maternal birth cohort and parity as confounders and thus as controlled. We also investigated the sex of twin pairs as an interactive variable, employing such methods as survival curve testing and using geometric, gamma, and exponential distributions where appropriate. The expectations derived from the mathematical models yield numerical estimates of fertility components. The results suggest that unlike-sex twin-prone mothers have higher fecundity than controls when they conceive singletons. Further, fecundity appears high and unimpaired before the birth of twins. Mothers of like-sex twins experience somewhat shorter and but more variable birth intervals than corresponding controls before the birth of twins, suggesting within-group heterogeneity. Specifically, the birth of like-sex twins is preceded by low fecundity and a short period of postpartum amenorrhea. Biologically, like-sex (presumably monozygotic) twin-prone mothers have a hormonal defect related eventually to menopausal status that interferes with ovulation and perhaps with lactation. As for unlike-sex twin-bearing mothers, they probably experience a displacement of their maximum fertility potential toward early reproductive life and an extension of their menstrual life. From a methodologic standpoint, the study of the fertility of twin-prone mothers cannot proceed without estimates of the fertility components of birth intervals, as these intervals do not lend themselves to straightforward analytical interpretations by statistical analyses.     

Attenuating the defeminization of the neonatal rat brain: Mechanisms of action of cyproterone acetate, 1,4,6-androstatriene-3,17,-dione and a synthetic progestin, R5020

Although defeminization of the rat brain appears to depend significantly on the conversion of testosterone (T) to estradiol (E₂), the antiandrogenic steroid cyproterone acetate (CA) is able to attenuate defeminization. In order to study the mechanism of action of CA on brain sexual differentiation, newborn male rats were given subcutaneous injections of this steroid on postnatal Days 2–6. When castrated on Day 70 and given estrogen and progesterone, these CA-treated males displayed elevated lordosis quotients (LQ) compared to controls. CA-treated neonatal males were also examined at the end of the drug treatment to ascertain the mechanism of drug action: (1) Serum T levels were normal; (2) Brain cell nuclear estrogen receptor occupation, estimated by an exchange assay, was reduced by ≈ 30% in the brains of the CA-treated males, although the ability of exogenous E₂ to occupy these brain estrogen receptors was not reduced. Other work has demonstrated a weak competitive effect of cyproterone on aromatization, and thus cyproterone acetate may have interfered with the conversion of T to E₂ CA also has progestogenic activity, and 5-mm capsules of a potent synthetic progestin, R5020, given to newborn male rats on Days 2–6, are shown to elevate the LQ after postnatal Day 70 to the same extent as CA. However, R5020 did not reduce estrogen receptor occupation in the neonatal male rat brain and was without effect on serum T levels in the neonatal male. Because of the implied role of T-derived estrogens in defeminization, an experiment was conducted showing that the defeminizing action of estradiol benzoate given to 3-day-old female rat pups is attenuated by the antiestrogen, CI628, and not by the potent inhibitor of aromatization, 1,4,6-androstatriene-3,17-dione (ATD). This result complements previous experiments showing that both ATD and CI628 attenuate the defeminization produced by T. Taken together, the results lend further support to a pivotal role for aromatization and for estrogen-receptor interactions in the defeminizing effects of T. The actions of progestins such as CA and R5020 in attenuating defeminization are discussed in relation to the recent demonstration of progestin receptors in the neonatal rat brain. It is concluded that CA may act by a combination of actions, both by inhibiting aromatization and by acting as a progestin.