Daphne M. Lawrence

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.

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 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.

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.

VIRILIZING OVARIAN HILUS CELL HYPERPLASIA WITH SPECIAL REFERENCE TO HORMONE EXCRETION

BERGER in 1923 observed that ovarian hilus cells are morphologically indistinguishable from Leydig cells, the testicular interstitial cells which are believed to be responsible for androgen production. He also noted their close association with non-myelinated nerve fibres and called them sympathicotropic cells. Hilus cells generally lie in the ovarian medulla. They are of variable size; typically they are ovoid, granular and eosinophilic. The nucleus is eccentric; it is reticular and there is usually at least one nucleolus. Lipids and lipochrome are commonly demonstrable in the cytoplasm. Reinke crystalloids may be present but are not necessarily characteristic of hilus cells. Sternberg (1949) found that hilus cells were present in 80 per cent of the normal ovaries which he examined. Hilus cell hyperplasia without signs of virilization has been observed by Brannan (1927) and Sternberg et al. (1953) to occur in pregnancy and in relation to the menopause. Active hilus cells are said to be an atypical finding in post-menopausal women (Berger, 1923). The demonstration of hyperplasia of the hilus cells depends on the presence of an excess of these cells in unencapsulated nests in the hilar region or in the ovarian cortex. It is difficult to make an unequivocal histological diagnosis without reference to serial sections of normal ovaries from patients of comparable age and reproductive status. Virilism in association with hilus cell hyperplasia has been reported by Sternberg (1949), Taliaferro et al. (1953), Langley (1954), Greenblatt et al. (1956) and Siganos (1961). The case of Joplin and Fraser (1962) appears to be identical with that of Siganos (1961). The virilism is of varying degree but may include hirsutism, male pubic hair distribution, masculine body build, deepening of the voice and enlargement of the clitoris (Table I). Hilus cell tumours associated with virilism have been recorded more frequently; series of cases have been reviewed by Merrill (1959), Novak and Mattingly (1960, and Siganos (1961). The cases of Plate (1957) and Goodwin et al. (1962) suggest that the tumours may occasionally be oestrogenic, though Novak and Mattingly (1960) considered that Plate’s case was one of luteinized granulosa-theca tumour. Hormone studies in cases of abnormal hilus cell proliferation associated with virilism have been very limited. Usually only 17-ketosteroid excretion (Table I) has been estimated. We have been unable to find any record of oestrogen determinations made by chemical methods. In the present case of virilism associated with hilus cell hyperplasia treated by wedge resection of the ovary detailed studies were made of preand post-operative hormonal excretion, and excessive production of both androgens and oestrogens was demonstrated.

Plasma Testosterone Using Sephadex LH-20 and Saturation Analysis by Competitive Protein Binding

A method Tor measuring plasma testosterone using separation on short columns of Sephadex LH-20 and competitive protein binding is described. This is more reliable and practicable than methods using paper or thin layer chromatography separation and Sephadex LH-20 can be re-used after washing.

STEROID EXCRETION IN THE STEIN-LEVENTHAL SYNDROME*

METHODS Twenty-four hour urine collections were made. Total urinary 17-ketosteroids and 17-ketogenic steroids were estimated by the method of Norymberski, Stubbs and West (1953). Fractionated 17-ketosteroids and pregnanetriol were hydrolyzed and extracted as in the method of Cox and Finkelstein (1957) and separated by alumina chromatography. Paper chromatography (Bush, 1952, 1954 and 1961) was used to separate the individual ketosteroids. Pregnanetrio1 was eluted from the alumina by using the modification of Leon and Bulbrook (1960) and estimated by the method of Stern (1957). Urinary pregnanediol was estimated by the method of Klopper, Michie and Brown (1955) and that of Brown (1955) for urinary oestrogens.

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.