Serum and seminal plasma hormonal profiles of infertile Nigerian male.

Male infertility constitutes a worldwide problem, especially in Nigeria where most men do not readily accept that they may contribute to the couple's infertility. In order to assess hormonal disturbances in the male infertility we compared male reproductive hormonal levels in human serum and seminal plasma and evaluated the hypothalamic-pituitary-testicular-axis in infertile Nigerian males. The biophysical semen parameters were assessed by W.H.O. standard manual method. Serum and seminal plasma male reproductive hormones (Leutinizing hormones, Follicular stimulating hormone, Prolactin and Testosterone) were measured by Enzyme Immunoassay (EIA) technique of W.H.O. in sixty (60) infertile adult male Nigerians (Oligospermic; n = 40 and azoopermic; n = 20) and forty controls of proven fertility (Normospermic subjects; n = 40). The results show that the serum concentrations of gonadotropins (LH and FSH) were significantly higher (P<0.05) in infertile subjects than controls. Patterns of serum prolactin levels were similar. The values of gonadotropins in serum were significantly higher (P<0.05) than those of seminal plasma. Seminal plasma testosterone in infertile subjects was significantly higher (P<0.005) than that of controls but the serum levels of testosterone were significantly higher (P<0.05) in azoospermic than oligospermic subjects and controls. There was no significant correlation between serum hormonal level and seminal plasma hormonal level in all the groups (P<0.05). We concluded that male infertility in Nigerians is characterized by hyperprolactinaemia, raised serum gonadotropins (LH, FSH), and raised seminal plasma testosterone. Hormonal profiles in serum and seminal plasma were not significantly correlated, and hence cannot be used as exclusive alternative in male infertility investigations. The observed spermogram in spite of significant elevation of seminal plasma testosterone in infertile males investigated suggests Sertoli cells malfunction.

Selenium status of idiopathic infertile Nigerian males.

Selenium concentration in the sera and seminal plasma of 60 infertile males (40 oligospermia and 20 azoospermia) and 40 males with proven evidence of fertility (normospermia; control group) were estimated using atomic absorption spectrophotometry. Results were correlated with spermatogram and hormonal levels in order to determine their relationship and significance in male infertility. The mean serum concentrations of selenium was found to be significantly increased in oligospermic compared to azoospermic subjects and controls (p < 0.01), whereas the seminal plasma level was significantly higher in azoospermic compared to oligospermic subjects and controls (p < 0.001). Thus, the ratio of serum selenium to seminal plasma selenium was 1: 1 in controls, 4: 1 in oligospermia, and 1: 2 in azoospermic subject.A significant inverse correlation was observed between serum selenium level and sperm count (p < 0.01). Similarly, seminal plasma selenium correlated with spermatozoa motility, viability, and morphology. Serum selenium level shows positive correlation with the serum testosterone level (p < 0.01). In conclusion, there appears to be a physiological balance in the distribution of selenium in serum and seminal plasma compartment of control males. A disturbance in this balance has a significant influence on spermatogenesis. Selenium appears to have a positive influence on Leydig cells, thus influencing the secretion of testosterone.

Hyperprolactinaemia as a cause of male infertility in Ibadan.

Sera from normospermic, oligospermic and azoospermic adult Nigerians were analysed by radioimmunoassay (RIA) for prolactin (PRL) and testosterone (T). The mean +/- SEM DRL concentration (M.I.U./L) of 1275.00 +/- 157.90 in azoospermics and 1165.50 +/- 181.50 in Oligospermics are significantly higher (P < 0.001) than 727.60 +/- 42.60 in normospermics. The mean +/- SEM T concentration (nmol/L) of 29.60 +/- 18.20 in azoospermics and 56.50 +/- 15.50 in Oligospermics are significantly lower (P +/- 0.001) than 258.60 +/- 62.20 in normospermics.

Seminal plasma zinc level in users of gossypol.

Seminal plasma zinc levels were determined in 13 healthy male volunteers on gossypol, a triterpenoid aldehyde extracted to purity from cotton plant which has been found to be an orally active male fertility regulation agent that is simple, economical and reversible. Each subject was given 20 mg gossypol tablet daily until azoospermia occurred. Thereafter, a maintenance dose of 7.5 mg or 10 mg of gossypol was given orally to alternate subject. Each subject was followed up monthly for one year. Serial semen analysis and seminal plasma zinc levels were determined prior to and after administration of gossypol monthly for 52 weeks. The mean sperm count and motility decreased significantly until azoopermia occurred in all subjects at about the 20th week of follow up. However, there was no significant difference in the mean seminal plasma zinc levels throughout the period of observation irrespective of the dosage regimen of gossypol used by the subjects. It was concluded that gossypol has no effect on the seminal plasma zinc level in users of gossypol.

The prevalence of insulin resistance and other cardiovascular disease risk factors in healthy elderly southwestern Nigerians.

We assessed the prevalence of coronary heart disease (CHD) risk factors including insulin resistance in 500 (205 males, 295 females) healthy elderly (age > 55 years) indigenous, low socioeconomic group Yorubas residents in either an urban slum (n = 240) or a rural town (n = 260) in southwestern Nigeria. Anthropometric indices, blood pressure and fasting plasma levels of glucose, lipids, insulin and insulin resistance were measured. The results indicated that: (i) gross obesity (4.4%), diabetes (1.6%), hyperlipidaemia (0.2%) and cigarette smoking (4.8%) were relatively uncommon in the population, although the prevalence of hypertension (30%) was higher than previously reported from this population; (ii). the subjects had a relatively high prevalence of multiple CHD risk factors (about 20% had > 4 risk factors), an observation considered paradoxical in view of the reportedly low CHD prevalence in this population; (iii) these CHD risk factors (increased body mass and blood pressure (BP), hyperinsulinaemia and insulin resistance) were more prevalent in the women and in urban residents; (iv) hyperinsulinaemia (20%) and insulin resistance (35%) were common in the population, and were associated, on regression analyses, to such other CHD risk factors as BP and body mass, particularly in women, suggesting, as in Caucasians, that insulin resistance could be an important index of CHD risk; and (v) the excess of multiple CHD risk factors in the women, is due at least in part, to their increased tendency to obesity (8%) and reduced physical activity (83%). This study concludes that: (i) despite the high prevalence of multiple risk factors in this population, CHD prevalence is low, indicating the supremacy of such major risk factors as diabetes and hyperlipidaemia (relatively uncommon here) in the development of CHD; and (ii) potentially the greatest CHD risk is in the elderly women especially if relatively overweight, physically inactive and resident in an urban centre. While further confirmatory studies are necessary in younger subjects and across societal socioeconomic strata, our results nonetheless suggest that attempts to maintain the CHD prevalence at low levels in this population should include efforts directed at reducing excess body weight particularly in women, and advice on maintenance of a traditional diet to keep lipid levels and diabetes prevalence low.

Biophysical and biochemical analysis of semen in infertile Nigerian males.

Biophysical analysis of semen was performed in fifty-eight Nigerian male partners of infertile marriages. Sperm count concentration was significantly higher (P < 0.001) in oligospermics compared to normospermics as expected. However, there was no significant difference in sperm volume or motility percentage between the normospermics and the oligospermics; of course, no sperms were seen in the azoospermics. Biochemical analyses of serum zinc, copper, magnesium, and manganese by atomic absorption spectrophotometry [8] were further correlated in fifty-two patients. There were no statistically significant differences observed in the serum levels of zinc, magnesium, and copper among the normospermics, oligospermics, and azoospermics. The normospermic infertile patients, however, exhibited higher serum manganese when compared with oligospermics and azoospermics (P < 0.001). This finding suggests a potential role for manganese in the evaluation of infertile males.

Apparent hypocalcaemia in Nigerian children with kwashiorkor.

Thirty children with kwashiorkor had a mean +/- SEM plasma calcium (Ca) of 7.15 +/- 0.10mg/100ml; total proteins (TP) of 4.60 +/- 0.17g/100ml and albumin (A) of 1.89 +/- 0.11g/100ml. These values are significantly lower (p < 0.001) than the corresponding values of 9.07 +/- 0.10; 7.30 +/- 0.11 and 3.85 +/- 0.07 observed in thirty other age-matched normal controls. No significant differences exist in the plasma alkaline phosphatase (AP) levels in both groups. Correction of calcium for hypoalbuminaemia in the kwashiorkor group revealed that the observed hypocalcaemia in kwashiorkor is merely apparent.

Insulin responses following glucose administration in menstruating women.

OBJECTIVE: The aim of the study was to investigate changes in insulin sensitivity during the menstrual cycle, in a group of regularly menstruating black African women. METHOD: Insulin responses to intravenous glucose (300 mg/kg) were assessed, for up to 3 h, in 3 groups of age- and body mass-matched non-obese sedentary Nigerian women: Group A, 7 women in the menstrual follicular phase; Group B, 7 women in the menstrual luteal phase; C, 7 men. RESULT: Women in the menstrual luteal phase had the greatest integrated first-phase insulin response and insulin/glucose ratios, much higher than the similar values for these variables obtained in other groups. This suggests that the menstrual luteal phase is associated with relative insulin resistance. CONCLUSION: Black African women in the menstrual luteal phase demonstrate an exaggerated insulin response to an acute glucose load and are thus relatively insulin-insensitive. This confirms previous observations in Caucasians.

Glucose and insulin responses to intravenous glucose challenge in relatives of Nigerian patients with non-insulin-dependent diabetes mellitus.

We analysed blood insulin and glucose concentrations before and during frequently sampled intravenous glucose tolerance tests (FSIGT) in 2 groups of Nigerian subjects: (A) Control group (n = 18), without a positive family history of diabetes mellitus, and (B) Experimental group (n = 16), comprising age-, sex- and body mass-matched first-degree relatives of patients with non-insulin-dependent diabetes mellitus (NIDDM). In comparison with Group A subjects, those in Group B had: (i) higher fasting plasma glucose level (mean +/- S.E.M. 4.1 +/- 0.1 vs. 3.8 +/- 0.11 mmol/l, P < 0.05); (ii) similar fasting serum insulin levels (6.7 +/- 5.0 vs. 5.8 +/- 5.6 mU/l, P = NS); (iii) lower mean incremental area under the first-phase (t = 0-10 min) post-glucose challenge insulin curve (376.9 +/- 8.8 vs. 435.6 +/- 5.6 mU/min l-1, P < 0.05); (iv) increased incremental area under the second-phase (t = 10-182 min) post-glucose challenge insulin curve (432.9 +/- 11.5 vs. 161.3 +/- 8.7 mU/min l-1, P < 0.05); (v) reduced KG rate constant of glucose elimination (0.97 +/- 0.12 vs. 1.41 +/- 0.12%/min, P < 0.05). These results suggest that the subjects with a positive family history of NIDDM have a reduced beta-cell insulin secretory reserve (from reduced first-phase insulin response), tendency to rebound hyperinsulinemia during the latter phase of the insulin secretory response, a degree of tissue insulin insensitivity (as evident from high fasting plasma glucose despite similar insulin levels) and a diminished glucose disposal rate, in comparison with subjects without a family history of NIDDM. These features predict subsequent development of diabetes and suggest that as in Caucasians, first-degree relatives of Nigerian patients with NIDDM are at greater risk for future development of the disease.

An analysis of the prolactin surge.

Daily sera from normally menstruating women analysed by radioimmunoassay (RIA) with prolactin kits from NIH showed midcycle prolactin elevations coinciding with LH surge. No such elevations were observed with Serono prolactin kit. Sera assayed both at NIH and Population Council laboratories confirmed the higher prolactin values measured by NIH kit. Evaluation studies showed no antisera contamination in both kits, but confirmed LH-contamination of the NIH hPRL VLS4 tracer. This may explain the reported wide prolactin variations.

Plasma and salivary concentrations of glucose and cortisol during insulin-induced hypoglycaemic stress in healthy Nigerians.

We measured cortisol levels in plasma and saliva samples obtained simultaneously from 10 fasting adult Nigerians at 0900 h and at 60 and 90 min of hypoglycaemia induced by intravenous insulin. Salivary glucose levels (fasting and after i.v. insulin) were unaffected by hypoglycaemia and did not correlate with plasma glucose at any time point. Cortisol levels in plasma and saliva increased by 50% and 120%, respectively, from fasting to 90 min values (both P less than 0.05) after i.v. insulin. This increase was evident by 60 min (plasma 33% and saliva 40%, both P less than 0.05 compared to fasting values). There was a significant positive correlation between the percentage increases in plasma and salivary cortisol (r = 0.65, P less than 0.05). Salivary cortisol was always (0900 h and during hypoglycaemic stress) 15-20% of total plasma cortisol, a percentage similar to the reported values on the contribution of free plasma cortisol to total plasma cortisol. We conclude that increases in plasma cortisol are reflected in saliva, and salivary cortisol could be estimated as an alternative to free plasma cortisol in the dynamic assessment of adrenocortical function in humans.

Heat-labile prolactin immunoreactivity in normal human tissues: artifacts of peptide hormone radioimmunoassay in human tissues.

We recently demonstrated that a substantial proportion of the previously reported widespread distribution of human chorionic gonadotropin-like material in nonplacental normal human tissues is due to non-specific activity of tissue proteases (Adejuwon & Segal, 1984). The study was extended to another polypetide hormone, measured by the same general method of radioimmunoassay. Normal tissue samples of colon (n = 1) and testes (n = 5) obtained at surgery were analysed by a highly specific and sensitive radioimmunoassay (RIA) for human prolactin (hPRL). All tissues investigated appeared to contain immunoreactive hPRL-like material (6.7 +/- 5.3 ng/g weight, mean +/- s.d.) Heat at 55 degrees C for 15-20 min was found to have no effect on the immunoreactivity of purified hPRL. Exposure of normal tissues to these conditions was, however, found to completely eliminate the hPRL-like immunoreactivity. The factor present in these normal tissues giving positive radioimmunoassay results for hPRL is not identical to native hPRL. It may be due to tissue proteases interfering with the radioligand assay. True polypeptide hormone immunoreactivity must be distinguished from proteolytic activity by treatment with heat or protease inhibitor.

Absence of chorionic gonadotropin in sera of women who use intrauterine devices.

A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the intrauterine contraceptive device (IUD). Starting on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, we collected daily blood samples from three groups of normally menstruating young women. The study groups were (A) IUD users (n = 30), (B) women with tubal ligation (n = 30), and (C) women trying to become pregnant (n = 15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. Two subjects who became pregnant, as judged by progressive increases in hCG and P levels in the luteal phase, belonged to the group planning pregnancy. The finding of two pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

PIP: A controlled study was undertaken to determine whether unnoticed pregnancies routinely occur in users of the IUD. Beginning on day 10 of the menstrual cycle and continuing through the onset of menstruation or until the diagnosis of pregnancy, the authors collected daily blood samples from 3 groups of normally menstruating young women. The study groups were: a) IUD users (n=30); b) women with tubal ligation (n=30); and c) women trying to become pregnant (n=15). The sequential serum samples were analyzed by radioimmunoassay for progesterone (P), human luteinizing hormone (hLH), and human chorionic gonadotropin (hCG). No positive hCG assays in luteal phase blood sera of IUD users were observed. The only positive hCG determinations of IUD users coincided with the preovulatory surge of hLH. 2 subjects who become pregnant as judged by progressive increases in hCG and P levels in the luteal phase belonged to the group planning pregnancy. The finding of 2 pregnancies in 15 months of exposure is consistent with the assumption of natural fertility. The probability of no pregnancies in 30 months at risk, as observed among the IUD users, is between 1 in 200 and 1 in 100,000, depending on the assumption made for natural fertility. The study demonstrates that IUD users do not retain their natural fertility, and that IUDs do not exert their antifertility effect as abortifacient agents. If a confirmed pregnancy is detected in an IUD user, it may be assumed to represent an isolated case of contraceptive failure.

Serum prolactin profiles of normal human conceptual cycles.

Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays (RIA) for prolactin (hPRL), estradiol-17 beta and luteinizing hormone (hLH). Two of the observed subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPRL were observed in either subject. Enormous spikes were observed in daily prolactin values, with wide variations between subjects.

PIP: Commencing on day 10 of the menstrual cycle through onset of subsequent menses, or confirmation of pregnancy, daily sera collected from 15 women planning pregnancy were analyzed by radioimmunoassays for prolactin (hPRL), estradiol-17beta, and luteinizing hormone (hLH). Two of the subjects became pregnant in the single cycles studied. The profiles of these hormones during the early gestation following spontaneous ovulation were established. No distinct midcycle peaks of hPRL were observed in either subject. Enormous spikes were observed in daily hPRL values, with wide variations between subjects.

Daily serum choriogonadotropin concentrations in early human gestation.

Fifteen regularly menstruating, healthy women were studied from day 10 of the menstrual cycle to either confirmation of pregnancy or spontaneous menses. Daily blood samples were obtained and serum luteinizing hormone (LH), human chorionic gonadotropin hormone (hCG), 17 beta-estradiol and progesterone were determined by means of specific radioimmunoassay (RIA). Two of the women experienced spontaneous conception with a rise in hCG on 12 and 13 days after LH peak.

Apparent chorionic gonadotropin immunoreactivity in human non-placental tissues: reduction by protease inhibitors or heat treatment.

Thirty-three of forty-one non-placental human tissue samples analysed by radioimmunoassay (RIA) appeared to contain immunoreactive hCG-like material. Tissues with apparent hCG in appreciable quantity were exposed to heat or protease inhibitors to ascertain the contribution of proteolytic enzyme activity to the observed immunoreactivity. Following incubation with protease inhibitor N-alpha-p-tosyl-L-lysine chloromethyl ketone-HCl (TLCK) at a dose that has no effect on the hCG standard curve and reduces the assayable hCG in term placenta by less than 20%, the hCG-like immunoreactivity of testicular and colon tissues was reduced by 39 to 90%. Similarly, heat treatment virtually eliminated hCG-like immunoreactivity of non-placental normal tissues, but had little effect on purified hCG or hCG present in term placenta. The factor present in normal non-placental human tissue giving positive results in the RIA for hCG is not identical to native hCG; it may be proteolytic in nature thus influencing the radioligand assay. The residual immunoreactivity measured following heat treatment of purified hCG increases when anti hCG-beta antiserum is used, but decreases when either anti hCG-alpha or anti-hCG is used.

Comparative prolactin profiles in IUD users and non-IUD users.

Starting from the 10th day of the menstrual cycle through onset of the subsequent menstrual bleeding, daily blood samples were collected from 14 women using Copper T IUDs and 10 normal control women. The serum samples were analysed by radioimmunoassay (RIA) for human prolactin (hPRL) and human luteinizing hormone (hLH). hPRL values were subjected to statistics. Episodic patterns of hPRL were observed for all subjects. IUD users show generally lower daily levels of hPRL than non-IUD users, but the apparent differences were statistically insignificant.

Effect of chloroquine administration on the in vitro conjugation of oestradiol-17 beta by rat liver.

The conjugation of oestradiol-17 beta was studied in control and chloroquine-treated rats. Liver homogenates were incubated with [14C]oestradiol-17 beta and cofactors for 4 h at 37 degrees C and free radioactivity was extracted before and after hot acid hydrolysis. The extent of conjugation was estimated from the ratio of free radioactivity to free plus conjugated radioactivity. The method was authenticated by the negligibly low conjugation obtained for either heat-denatured homogenates or water blank. Each experiment was corrected for its own recovery. The effects of both single and multiple intramuscular injections of chloroquine phosphate to rats on the in vitro conjugation of oestradiol-17 beta were studied separately. It was observed that both procedures significantly potentiated conjugation.

Pituitary-ovarian function after tubal ligation.

Pituitary-ovarian function was evaluated by measurement of daily serum levels of luteinizing hormone (LH), 17 beta-estradiol, and progesterone in women with a previous history of tubal ligation. Normally menstruating women served as controls. The duration of the proliferative and luteal phase was similar for both groups. The midluteal progesterone level averages did not differ between the two groups. Preovulatory LH and 17 beta-estradiol peaks were significantly lower in the tubal ligation group; average midluteal LH and 17 beta-estradiol levels were also lower. These results reveal that pituitary-ovarian function can be altered following surgical sterilization.

PIP: Menstrual disorders have been reported following tubal surgery. This study investigates luteinizing hormone (LH), 17beta-estradiol, and progesterone levels in 30 women (age range, 24-38 years; average age, 32 years), who had had elective tubal ligation for fertility control. Elective surgical sterilization was performed between 1 month and 8 years previously. The controls consisted of 15 normally menstruating women (aged 20-32 years; average age, 24), seeking to become pregnant who had not used either oral contraceptives or IUDs for at least 1 month before the study. Daily blood samples were collected starting from day 10 of the menstrual cycle until the onset of the next menstruation. Case selection and specimen collections were done in Santo Domingo, Dominican Republic. Hormone determinations by radioimmunoassays were done on a double-blind basis at the Population Council in New York. Progesterone and 17-b estradiol were determined by radioimmunoassay according to the method of Thorneycroft and Stone, while human luteinizing hormone (hLH) was measured by the double antibody technique of Vaitukaitis et.al. Average duration of the proliferative and luteal phase were 14.4 + or - 3.0 and 13.3 + or - 2.9 days, respectively, for the control group and 13.5 and 2.4 and 14.2 + or - 1.7 days for the women with tubal ligation. The total length of the cycle, 27.7 days, is the same for both groups. The midluteal progesterone level averages did not differ between the 2 groups, although when the controls were compared with tubal ligated women 30 years of age or younger, the difference was significant. Preovulatory LH and 17beta-estradiol peaks were significantly lower in the tubal ligation group, as were the average midluteal LH and 17beta-estradiol levels. These results suggest that surgical sterilization can result in subtle changes in ovarian function, even though ovulation itself is not affected. Bleeding irregularities following tubal ligation may in part be due to the fact that different surgical procedures may have different effects on ovarian blood supply. Further research should be done to compare specific effects of different sterilization procedures on ovarian function.

Pituitary and placental hormone levels in pseudocyesis.

Twelve patients with clinical features of pseudocyesis were divided into two groups according to the presence or absence of galactorrhea. The mean serum prolactin level of patients with galactorrhea was significantly higher than the normal values of the patients without galactorrhea. The mean serum levels of luteinizing hormone and follicle-stimulating hormone were markedly elevated in patients without galactorrhea. This was especially true of luteinizing hormone. Serum levels of human chorionic gonadotropin were undetectable in all patients. The significance of these observations is discussed.