H. H. G. Mcgarrigle

REDUCED SEX HORMONE BINDING GLOBULIN AND DERIVED FREE TESTOSTERONE LEVELS IN WOMEN WITH SEVERE ACNE

Reduced circulating sex hormone binding globulin (SHBG) levels were found in 54% of a group of women with moderate to severe acne and in 60% of another group of twenty‐three women who had acne complicated by hirsutism and/or irregular menstrual cycles. The concentrations of SHBG for the women with acne alone (mean 48 ± 24 nmol/l) and for those with acne and hirsutes (mean 39 ± 18 nmol/l) were compared with the SHBG concentrations of fifteen unaffected women with normal menstrual cycles (mean 70 ± 19 nmol/l). The differences in mean SHBG values for both groups of women with acne were significant (P < 0·001) on comparison with the mean for the unaffected women.

Diurnal variation of plasma and saliva oestrogen, progesterone, cortisol and plasma dehydroepiandrosterone sulphate in late pregnancy

The diurnal variation of plasma oestrone (E1), oestradiol (E2), oestriol (E3), progesterone (P), cortisol (F) and dehydroepiandrosterone sulphate (DHAS) and saliva E1, E2, E3, P and F was investigated in matched plasma, and saliva samples were obtained hourly from 08.00 to 24.00 h and at 04.00, 07.00 and 08.00 h from nine pregnant women (3 at 30, 3 at 34 and 3 at 38 weeks gestation). A diurnal variation in plasma and saliva cortisol levels was found in all subjects and in plasma DHAS in 8 out of 9 subjects. No consistent diurnal variation was found at any gestation in any of the other hormones in plasma or saliva. There was a significant correlation between saliva E3 and P levels at 30 weeks gestation but no other consistent correlations between hormone levels were found at any gestation.

Induction of Ovulation in Women with Hyperprolactinemic Amenorrhea Using Clomiphene and Human Chorionic Gonadotropin or Bromocriptine

Clomiphene citrate (Clomid), when given alone, is generally considered ineffective in inducing ovulation in women with hyperprolactinemia. This study reports the treatment of 29 infertile women with hyperprolactinemic amenorrhea. Twenty-one patients (eighteen of whom had previously had no ovulation response to Clomid alone) were treated with a combined regimen of Clomid (100 to 200 mg/day for 5 days) and two injections of 5000 IU of human chorionic gonadotropin (HCG), the first 8 to 10 days after Clomid withdrawal and a second injection 1 week later. Basal body temperature charts, conception, and/or plasma progesterone measurements showed that 19 patients ovulated (90%). There were 17 pregnancies in 12 of 21 patients (57% pregnancy rate) with 15 single live births and two abortions. When bromocriptine (Parlodel) became available, a total of 22 patients (including 14 patients previously treated with Clomid/HCG, six of them successfully) with amenorrhea associated with hyperprolactinemia were treated with this drug with dosages varying from 2.5 mg to 15 mg/day. Ovulation was confirmed in 20 patients (90%). There were 17 pregnancies in 15 patients (68% pregnancy rate) with 15 single live births and two first-trimester abortions. In all, 21 of 29 patients (73%) achieved one or more pregnancies resulting in live births with one or both of the above treatments. It is concluded that a combined Clomid/HCG regimen can often be used as an effective alternative to bromocriptine therapy in the treatment of infertility associated with hyperprolactinemic amenorrhea.

Plasma oestradiol and progesterone estimation for the monitoring of induction of ovulation with clomiphene and chorionic gonadotrophin.

Two hundred and thirty‐five courses of treatment with clomiphene and human chorionic gonadotrophin (HCG) were administered for the induction of ovulation in 75 infertile women (three with primary amenorrhoea, 45 with secondary amenorrhoea and 27 with oligomenorrhoea) of whom 61 had previously been unsuccessfully treated with clomiphene alone. The treatment was monitored by plasma oestradiol estimations on day 15 and day 22 in 103 cycles and by plasma progesterone estimations on day 22 in all 235 cycles. Injections of HCG were given on days 15 and 22. Twenty patients failed to respond to treatment (43 courses). The remaining 55 patients showed no response in 32 courses, deficient responses in 55 cycles and adequate responses in 105 cycles (plasma progesterone level exceeding 10 ng per ml on day 22). The mean values (±D) of plasma oestradiol on day 15, reflecting follicular development, were: 73±30 pg per ml for cycles with no response; 255±182 for deficient cycles and 366±226 pg per ml for adequate cycles. There was a positive correlation (r =0±57) between day 15 plasma oestradiol and day 22 plasma progesterone values. Increased clomiphene dosage resulted in higher plasma oestradiol and progesterone levels. Thirty‐nine pregnancies occurred in 34 out of 55 patients capable of response (62 per cent). The plasma progesterone levels during conception cycles were higher than those in non‐conception cycles in the same patients. Monitoring of induction of ovulation by plasma hormone estimations allows detection and correction of inadequate response.

PLASMA TESTOSTERONE AND ANDROSTENEDIONE LEVELS DURING MONITORED INDUCTION OF OVULATION IN INFERTILE WOMEN WITH ‘SIMPLE’ AMENORRHOEA AND WITH THE POLYCYSTIC OVARY SYNDROME

Twenty‐seven infertile patients with ‘simple’ amenorrhoea‐oligomenorrhoea and eighteen with the polycystic ovary (PCO) syndrome were treated for induction of ovulation with clomiphene, human menopausal gonadotrophin and human chorionic gonadotrophin. The treatment was monitored by plasma oestradiol, testosterone, andfostenedione and progesterone estimation. Women with PCO had significantly higher plasma androgen levels than women with ‘simple’ amenorrhoea (P < 0.01 to P < 0.001) both before treatment and during induction of ovulation. When ovulation was induced the pregnancy rate for women with the PCO syndrome with elevated androgens was 21% while for those with uncomplicated amenorrhoea it was 75%. It is concluded that high levels of circulating androgens might be a factor preventing conception in some patients in whom ovulation is apparently successfully induced.

INDUCTION OF OVULATION WITH CLOMIPHENE AND HUMAN CHORIONIC GONADOTROPHIN IN WOMEN WITH HYPERPROLACTINAEMIC AMENORRHOEA

Seventeen women complaining of infertility (one with primary amenorrhoea, 14 with secondary amenorrhoea, and two with oligomenorrhoea) all had hyper‐prolactinaemia and were treated with clomiphene citrate and human chorionic onadotrophin (HCG), and plasma oestradiol, FSH and LH levels were measured. Although adequate pre‐ovulatory oestradiol levels were present, the surge of LH was absent until the injection of HCG after which all patients ovulated. There were 12 pregnancies in 9 patients resulting in 10 full‐term livebirths, one premature livebirth and one continuing pregnancy. The relevance of these findings to the possible role of prolactin in amenorrhoea is discussed.

THE MONITORING OF GONADOTROPHIN THERAPY BY PLASMA OESTRADIOL AND PROGESTERONE DETERMINATIONS

Plasma oestradiol and progesterone determinations by competitive protein binding techniques were introduced as a means of monitoring treatment with human gonadotrophins of 32 infertile women with amenorrhoea or severe oligomenorrhoea. Human menopausal gonadotrophin (HMG) was administered on days 1, 3 and 5. Human chorionic gonadotrophin (HCG) was injected on day 8 if the response to HMG stimulation was adequate but not excessive, a second dose being given seven days later.

PROLACTIN AND LUTEAL INSUFFICIENCY

The relationship between mid‐luteal plasma levels of progesterone and prolactin was studied in 75 women with regular menstrual cycles. Eighteen women had normal prolactin (mean 260 ± 51.7 mU/l) and normal progesterone levels (mean 67 ± 21.3 nmol/l). Thirty‐nine women had elevated prolactin levels (mean 850 ± 503 mU/l); progesterone levels were normal in all cases (mean 61 ± 22.3nmol/l). Eighteen women had evidence of luteal deficiency (mean progesterone 15.3 ± 7.7 nmol/l); prolactin levels were normal in all cases (mean 243 106 mU/l). There was no correlation between plasma prolactin and progesterone levels.

A comparison of serial ultrasound measurements of fetal adrenal glands with maternal plasma and saliva oestriol and progesterone levels in normal pregnancy

SummaryThe purpose of the study was to assess the feasibility of making measurements of fetal adrenal glands using ultrasound and to determine whether there is any correlation between such measurements and maternal oestriol levels. Serial measurements of fetal adrenal and renal maximum transverse diameters, circumference and area, and maternal plasma and saliva oestriol and progesterone levels were made at 4 weekly intervals from 24 weeks to delivery in 32 normal pregnant women. There was an approximately linear increase in the fetal adrenal and renal measurements that were studied. There was no correlation between these measurements and either plasma or saliva oestriol or progesterone levels, or the saliva oestriol:progesterone ratio, at any specific gestation.

THE TREATMENT OF MILD ADRENAL HYPERPLASIA AND ASSOCIATED INFERTILITY WITH PREDNISONE

Thirty patients with mild post-pubertal adrenal hyperplasia, characterized by raised urinary 17-oxosteroid levels and variable combinations of irregular menses, hirsuties, infertility, and spontaneous abortion, were treated with 2.5 to 10 mg of prednisone per day and all conceived (55 pregnancies). With this treatment, regular, ovulatory cycles occurred immediately in 25 patients, and after two to six months, in the rest. Treatment reduced raised 17-oxosteroid levels to normal and brought about some improvement in hirsuties and acne. Forty-seven pregnancies ended in the birth of liveborn infants; one of these died of prematurity and another had congenital emphysema. One pregnancy was terminated, two were of unknown outcome and five (9.4%) ended in abortion. Before treatment, 20 out of 22 pregnancies (91%) had ended in abortion.