Michael J. Diver

Diurnal rhythms of serum total, free and bioavailable testosterone and of SHBG in middle-aged men compared with those in young men

background Conflicting views are reported on the association between advancing age and gradually diminishing concentrations of serum total testosterone in men. The putative loss of diurnal rhythm in serum total testosterone in older men is reported to be in part due to low concentrations in the morning when compared to concentrations found in young men. We have measured total, free and bioavailable testosterone along with SHBG in samples taken every 30 min throughout a 24‐h period in 10 young and eight middle‐aged men.

The role of a single progesterone measurement in the diagnosis of early pregnancy failure and the prognosis of fetal viability

Objective To assess the role of a single maternal serum progesterone measurement in the immediate diagnosis of early pregnancy failure and in the long term prognosis of fetal viability.

Effect of menstrual cycle phase on the concentration of bioavailable 17-β oestradiol and testosterone and muscle strength

To investigate the effect of changes in sex hormone concentration on muscle strength and the bioavailability of 17-beta oestradiol (oestradiol) and testosterone, seven eumenorrheic females were tested during two phases of the menstrual cycle. Maximum voluntary isometric strength of the first dorsal interosseus muscle was measured during the early follicular and mid-luteal phases of the menstrual cycle. These phases were chosen for testing as the concentration of total oestradiol is significantly different in these two phases. Total oestradiol has been repeatedly associated with changes in muscle strength in females, whereas the effects of bioavailable oestradiol are unknown. The concentrations of total and bioavailable oestradiol and testosterone were measured in addition to the concentration of total progesterone. Concentrations of total progesterone and oestradiol were significantly different between the early follicular and mid-luteal phases of the menstrual cycle (P <0.05 and P <0.001 respectively). The concentration of total testosterone (0.7+/-0.2 and 0.8+/-0.1 nmol.l(-1) respectively) and the ratio of total oestradiol to progesterone (153.0+/-251.2 and 108.5+/-27.8 respectively) did not change significantly between the early follicular and mid-luteal phases. Bioavailable testosterone (102.2+/-66.3 and 105.0+/-90.2 pmol.l(-1) respectively) and bioavailable oestradiol (90.5+/-35.5 and 120.0+/-60.6 pmol.l(-1) respectively) did not differ significantly between phases. There were no significant differences in muscle strength during the menstrual cycle (P =0.1). Mean maximum voluntary isometric force of the first dorsal interosseus muscle did not correlate significantly with the mean concentration of any reproductive hormone measured. These results indicate that cyclical variation in endogenous reproductive hormones does not affect muscle strength.

PLASMA OESTRIOL AND HUMAN PLACENTAL LACTOGEN MEASUREMENTS IN PATIENTS WITH HIGH RISK PREGNANCIES

Maternal plasma oestriol and human placental lactogen (HPL) were measured serially in 383 at‐risk pregnancies. Eighty‐five infants were growth retarded and 122 developed fetal distress or neonatal asphyxia. Of the infants whose mothers had either abnormal plasma oestriol or HPL levels, 58 per cent were growth retarded, while 65 and 73 per cent in each group respectively developed fetal distress. The incidence of fetal complications when both plasma oestriol and HPL were abnormal was consistently greater than 66 per cent.

Plasma progesterone levels as an index of ovulation

Summary. Plasma progesterone levels were measured in three groups of untreated women. (1) Nine women with follicle rupture, proved by laparotomy or laparoscopy, had values of ≥40 nmol/l on days 18–24 (days −10—5 from the next period); thus a value of <40 nmol/1 should not be taken as evidence of ovulation. (2) Nineteen healthy women with normal menstrual histories had hormone assays on alternate days during one cycle. In five of them all values were <38 nmol/1. (3) Forty women had a single progesterone assay on days 20–29 of a conceptual cycle. Eight of them had a level <40 nmol/l. Ovulation had certainly occurred in all of them, but it is difficult to assess whether the sample timing was optimal since there was no following menstrual period. Progesterone levels in drug‐induced conceptual cycles were in general higher than those in spontaneous pregnancy cycles. Women with luteinization of the unruptured follicle frequently had values of >40 nmol/l. Conversely, a secretory endometrium was not uncommon in cycles with values of <38 nmol/l.

The long-term stability in whole blood of 14 commonly-requested hormone analytes.

Concentrations of 14 commonly-requested plasma hormones were measured in octuplicate in each of six subjects to determine their stability when unseparated from red cells for periods up to 1 week. Most of the analytes were stable when stored in this way and although statistically significant changes were recorded, in the great majority of cases the changes seen would have no bearing on the clinical interpretation of the result. In the light of these findings, we would confidently report results of analyses for these hormones in plasma that had remained in contact with red cells at ambient temperature for long periods of time.

Short-term changes in asymmetry and hormones in men

Abstract Asymmetries are negatively associated with developmental precision. However, asymmetries in human traits, which consist partly or entirely of soft-tissue, are correlated with a surprising diversity of fitness domains, including fertility, disease resistance, running speed, aggression, and depression. We show that in men there are both between-subject differences in asymmetry and short-term (24 h) within-subject changes in soft-tissue asymmetry, and the latter are more pronounced in some subjects than in others. A number of hormones showed significant correlations with these changes, including positive associations between asymmetry and luteinising hormone (LH), total thyroxine (T4), and parathyroid hormone (PTH), and negative associations between asymmetry and follicle stimulating hormone (FSH). “Fixed” asymmetries accumulated during development represent long-term developmental imprecision and are related to various stressors. Nonfixed asymmetries in soft-tissue traits may correlate with short-term changes in hormone concentrations. We discuss the implications of our findings for the understanding of the relationships between asymmetry, behaviour, and fitness in men, and the possible patterns of short-term changes in asymmetry in male and female partners.

POTENTIAL USES OF HUMAN PANCREATIC GROWTH HORMONE‐RELEASING FACTOR 1‐44 AMIDE

A family of growth hormone releasing peptides have been isolated and characterized from human pancreatic islet cell tumours. We have compared the growth hormone release in normal volunteers and patients with various hypothalamo‐pituitary disorders, following direct stimulation of the pituitary using 50μg of the most potent homologue, hp GRF 1‐44 amide i.v. with that following indirect stimulation using oral clonidine 0‐15 mg/m2, which depends on intact hypothalamic mechanisms. These tests both produced a wide variation in GH response in normal volunteers, considerable GH release following hp GRF 1^44 amide but little after clonidine in idiopathic GH deficiency, and indistinguishable, negligible responses in patients with craniopharyngiomas and pituitary tumours associated with GH deficiency. Two untreated acromegalics showed GH increments in the normal range despite elevated basal levels. It is concluded that hp GRF 1‐44 amide is of limited diagnostic value by itself, but may be of considerable therapeutic use in patients with idiopathic GH deficiency.

Effects of supra-physiological changes in human ovarian hormone levels on maximum force production of the first dorsal interosseus muscle

The purpose of this study was to investigate the effects of supra‐physiological changes in ovarian hormone levels on maximum force production in two conditions, one physiological (pregnancy) and one pseudo‐physiological (in vitro fertilization (IVF) treatment). Forty IVF patients were tested at four distinct stages of treatment and 35 women were tested during each trimester of pregnancy and following parturition. Maximum voluntary isometric force per unit cross‐sectional area of the first dorsal interosseus muscle was measured. Plasma concentrations of total and bioavailable oestradiol and testosterone were measured, in addition to the total concentrations of progesterone and human chorionic gonadotropin. Despite significant changes in the concentrations of total progesterone, 17β‐oestradiol, bioavailable oestradiol and testosterone between phases, strength did not change significantly throughout IVF treatment (1.30 ± 0.29, 1.16 ± 0.38, 1.20 ± 0.29 and 1.26 ± 0.34 N mm−2, respectively, in the 4 phases of IVF treatment). Force production was significantly higher during the second trimester of pregnancy than following childbirth (1.33 ± 0.20 N mm−2 at week 12 of pregnancy, 1.51 ± 0.42 N mm−2 at week 20, 1.15 ± 0.26 N mm−2 at week 36 and 0.94 ± 0.31 N mm−2 at week 6 postnatal) but was not significantly correlated with any of the hormones measured. These data suggest that extreme changes in the concentrations of reproductive hormones do not affect the maximum force‐generating capacity of young women.

The effect of clomiphene citrate treatment on cervical mucus and plasma estradiol and progesterone levels

OBJECTIVES To study the relationship between cervical mucus (CM) quality, postcoital test (PCT) results and plasma estradiol (E2) in clomiphene citrate (CC)-treated women. A subsidiary aim was to study the relationship between CM quality and plasma progesterone (P). DESIGN Untreated women were compared with oligo-ovulatory patients given CC. SETTING Infertility Clinic, Fazakerley Hospital, United Kingdom. PATIENTS, PARTICIPANTS Fifty-one untreated patients and 31 women given CC. INTERVENTIONS The treated women were given 50 mg/d CC from days 2 to 6 of their cycle. MAIN OUTCOME MEASURES A CM assessment, a PCT, plasma E2, and P were performed at the anticipated time of ovulation based on at least two previous basal body temperature charts and menstrual patterns. RESULTS In untreated women there was a very strong tendency for CM quality to improve with rising plasma E2 levels and to worsen with rising plasma P levels. There was a significant association between CM quality and PCT results. Similar results were found in CC-treated women, except that plasma E2 was very significantly higher and there was a significant inverse relationship between plasma E2 and CM quality. CONCLUSION High plasma E2 in the periovulatory phase in CC-treated women is a marker for increased sensitivity to and continuing action of the antiestrogen. This impairs the quality of the CM.