Morrie M. Gelfand

SEX STEROIDS AND AFFECT IN THE SURGICAL MENOPAUSE: A DOUBLE-BLIND, CROSS-OVER STUDY

The effect of estrogen and/or androgen on mood in surgically menopausal women was investigated with a prospective, double-blind, cross-over design. Oophorectomized women who received either estrogen (E), androgen (A), or a combined estrogen-androgen preparation (E-A) parenterally attained lower depression scores during both treatment phases compared to a placebo group (PL), coincident with their higher plasma estrogen and testosterone levels. When steroids were withdrawn, depression scores of all oophorectomized women were significantly higher than those of a hysterectomized control group with intact ovaries (CON). The A group also had higher hostility scores than the E, PL, and CON groups. These data provide evidence of a covariation between circulating levels of estrogen and testosterone and certain affects in healthy women.

Androgen and estrogen-androgen hormone replacement therapy: a review of the safety literature, 1941 to 1996

The endocrine physiology of the climacteric supports a rationale for the concomitant replacement of androgen and estrogen following menopause. Clinical and research experience with estrogen-androgen hormone replacement therapy, as well as androgen-only therapy, suggests that the health benefit offered by androgen replacement exceeds the potential risk when treatment is properly managed. In this review, we concentrate on the effects of oral alkylated androgens. The virilizing effects (e.g., hirsutism, acne, voice change, and alopecia) of oral androgens are typically dose and duration dependent; androgen replacement at doses < or = 10 mg once daily administered for prolonged periods (> 6 months) produces masculinization effects that generally abate with dose reduction or discontinuation of treatment. No clinical sequelae or irreversible pathophysiologic effects have been associated with any virilization that may occur. Changes in lipoprotein metabolism associated with oral estrogen-androgen use include reduced total cholesterol levels and reduced high-density lipoprotein cholesterol levels which may reduce the long-term risk of cardiovascular disease. No clinically identifiable risk with respect to other cardiovascular variables, such as blood pressure, has been associated with the longterm administration of low doses of oral androgen. With regard to liver toxicity, reports of jaundice, peliosis hepatis, and hepatocellular carcinoma are extremely rare at the dose levels of androgen used in hormone replacement therapy, although individual sensitivity to the potential hepatotoxic effects of oral alkylated and nonalkylated androgen may vary considerably. Daily dosing with oral alkylated androgen in combination with estrogen is well tolerated. Retrospective and prospective studies involving the use of androgens alone and in combination with estrogens demonstrate that concerns about the adverse effects of androgen use associated with supraphysiologic, self-escalated doses in men do not apply to the much lower doses combined with estrogens for hormone replacement in postmenopausal women.

Studies in placental permeability. Transmission of poliomyelitis antibodies, lipoproteins, and cholesterol in single and twin newborn infants.

I N PKE VI0 U s papers, we have compared the electrophoretic pattern in parturient and cord blood in normal and in pathological pregnancies1 There is a significant increase of the relative level of fetal y globulin as compared to the maternal y globulin level. This relative hypergammaglobulinemia of the newborn has been considered as an indication of its physiologic maturity. Transfer of the maternal y globulin to the fetus starts toward the sixth month of the pregnancy; its rate is different from that of the other serum proteins. Indeed, whereas the albumin and the other fractions are transferred at approximately the same rate throughout the last trimester, the rate of transfer of the y fraction is very low at the beginning (16 to 20 per cent of the maternal value), but it increases sharply and reaches the maternal level during the eighth month; the fetal level then exceeds the maternal level, so that at term the ratio of fetal/maternal y globulin is 1.35-1.50.

Studies on beta thalassemia trait in pregnancy

Abstract Beta thalassemia trait ranks second to iron deficiency as the most frequent cause of anemia of pregnancy in our clinic. The anemia of patients with thalassemia trait increases during the second trimester, as does that with normal controls. This is not sufficient to result in any disability or to require blood replacement during pregnancy. There were no adverse effects noted in any of the patients or in any of their infants. Investigation for the presence of thalassemia is required in all patients in whom the racial origin indicates a high incidence of the disorder. Although prophylactic oral iron therapy is warranted during pregnancy, it is necessary to guard against excessive and parenteral iron therapy which may lead to a state of iron overload in patients with thalassemia.

Individual differences in mood with menopausal replacement therapy: possible role of sex hormone-binding globulin

Ten surgically menopausal women who had been chronically receiving a combined estrogen-androgen preparation as replacement therapy showed an inverse relationship between plasma sex hormone levels and mood (P < 0.02). Our findings also suggest that measurement of sex hormone-binding globulin may be an important factor in explaining differential clinical response to hormone replacement therapy in postmenopausal women.

Incidence of Respiratory Distress Syndrome following Antenatal Betamethasone: Role of Sex, Type of Delivery, and Prolonged Rupture of Membranes

Premature male infants have a higher incidence of respiratory distress syndrome (RDS) than female infants (male/female = 1.7:1.) With the demonstration that antenatal use of betamethasone significantly reduces the incidence of RDS, a proportional reduction or possibly a complete elimination of the discrepancy between the two sexes might be expected. The role that sex, type of delivery, and prolonged rupture of membranes (PROM) may play in the development of RDS was tested in a prospective study of RDS prevention with betamethasone. A full course of betamethasone, ie, 12 mg, 24 hours apart, was given antenatally to 94 infants of 27 to 34 weeks gestation. The incidence of RDS in male infants was 29.1% vs 8.6% in female infants (P less than .02). The incidence of RDS among male babies delivered by cesarean section (30.3%) or vaginally (29.7%) was not statistically different, nor was there a difference between those with PROM greater than 24 hours (26.9%) and those without PROM (31.8%). The same was true of the incidence of RDS among female infants: cesarean section (14.2%) vs vaginal delivery (6.2%) and PROM greater than 24 hours (8%) vs (9.5%) without PROM. We conclude that: (1) Prevention of RDS with betamethasone is far more effective in female infants. The natural ratio of male/female of 1.7:1 becomes 3.4:1. (2) Once lung maturity has been achieved with betamethasone, the type of delivery plays no role in the development of RDS. (3) PROM does not add extra protection from RDS in the 27- to 34-week gestational age range.

The Antenatal Use of Betamethasone in the Prevention of Respiratory Distress Syndrome: A Controlled Double-blind Study

One hundred forty-six pregnant women were enrolled in a prospective double-blind study to assess the effectiveness and side-effects of antenatal administration of betamethasone in the prevention of respiratory distress syndrome (RDS) in potentially premature infants. On admission to the study, the women were given, at random, either 12 mg of betamethasone or placebo. The same dose was repeated 24 hours later and then weekly up to 34 weeks of gestation. Gestational age of the infants ranged from 25 to 34 weeks, and birth weights ranged between 730 and 2,650 gm. Statistically significant differences in favor of the infants in the betamethasone group were found in the incidence of RDS, 20.7% in the betamethasone group compared with 59.5% in the control group (P less than .005); in the severity of RDS (P less than .05); and in the death rate (P less than .05). A higher incidence of hypoglycemia was found among infants in the betamethasone group (P less than .05). Prolonged rupture of the membranes played no protective role against RDS, and the incidence of infection was similar in both groups.