Effect of pituitary gonadotrophins on proliferation of primary cultures of human ovarian stroma

Proliferation of ovarian stromal cells is a common phenomenon in peri- and post-menopausal ovaries. It is generally assumed to be secondary to the rise in circulating gonadotrophins at the menopause, though the process by which it occurs is poorly understood. This study aimed to examine the effect of menopausal levels of pituitary gonadotrophins on the growth of primary cultures of ovarian stroma. A culture system was developed using primary explants of ovarian stroma on a collagen substrate. The effect of follicle stimulating hormone (FSH; 10(-5) g/l) and luteinizing hormone (LH; 10(-5) g/l) on the proliferation of cultures derived from the cortices and medullae of ten ovaries was evaluated using a dual radiothymidine labelling technique. FSH was stimulatory to cortical cultures from 9/10 ovaries and medullary cultures from 7/10 ovaries, while LH was stimulatory to cortical cultures from 6/9 ovaries and medullary cultures from 5/10 ovaries. The responsiveness of the cultures did not correlate with the degree of hyperplasia in vivo. This study demonstrates that pituitary gonadotrophins may modulate the growth of stromal cells in culture, and thus may play a role in the process whereby stromal proliferation occurs in peri- and post-menopausal ovaries.     

The economic consequences of multiple gestation pregnancy in assisted conception cycles

This study estimates the projected costs of multiple births resulting from assisted conception cycles (in vitro fertilization with or without intracytoplasmic sperm injection and ovarian stimulation with gonadotrophin). The estimates are modelled from the volume of services, treatment success and multiple gestation rates in recent registry data. The coverage is restricted to hospital costs associated with delivery and the trends are projected to 2000 in the United States. Sensitivity analyses tested different assumptions about per annum trends in effectiveness, multiple pregnancy rates and health costs. The national cost of in vitro fertilization cycles is US$470.2 million (£313.5 million) and the cost of the multiple pregnancies from in vitro fertilization is US$639.9 million (£426.7 million). The national cost of ovarian stimulation cycles is US$166.6 million (£111.1 million) and the cost of the multiple pregnancies from ovarian stimulation is US$257.3 million (£171.6 million). Although costs are a limited indicator of the burden of illness, the projected national cost of multiple pregnancy associated with assisted conception in 2000 is greater than the base cost of the treatment. Prevention of multiple pregnancy in assisted conception cycles should be a priority.     

Hypogonadism in male outpatients with sarcoidosis

Hypogonadism is assumed to be present in sarcoidosis. Nevertheless, a comparison of circulating sex hormone concentrations of male sarcoidosis patients with those of healthy men has never been done. Moreover, it remains unknown if hypogonadism may contribute to a reduced muscle function, exercise intolerance, diminished vitality and depressed mood in male sarcoidosis patients. Pulmonary function, muscle function, exercise tolerance, vitality, mood, circulating sex hormone concentrations and C-reactive protein were assessed in 30 male sarcoidosis patients and 26 age-matched men with a normal pulmonary function. On average, patients had a restrictive pulmonary function, worse inspiratory and quadriceps muscle function, functional exercise intolerance, diminished vitality, depressed mood and increased systemic inflammation. Moreover, patients had significantly lower circulating (free) testosterone concentrations, while circulating sex hormone-binding globulin tended to be lower (p=0.0515). Circulating gonadotrophin concentrations were comparable. Non-significant relationships were found between sex hormones, clinical outcomes and C-reactive protein in patients with sarcoidosis. A significant number of male outpatients with sarcoidosis (46.7%) had low circulating testosterone concentrations, which was most probably caused by hypogonadotrophism. The clinical relevance of hypogonadism in male outpatients with sarcoidosis, however, remains currently unknown. Indeed, poor inspiratory and quadriceps muscle function, exercise intolerance, diminished vitality and depressed mood were not related to hypogonadism in these patients.     

Absence of systemic hormonal effects in an oestradiol diether topically active on the vaginal mucosa

The women in this study were either post-menopausal or ovariectomised for at least 1 yr prior to the study. They had also been treated for cancer of the cervix (27 women), endometrium (5), ovaries (5) or breast (1). All women presented with sexual troubles, mainly genital discomfort (dyspareunia or vaginism). In a double-blind fashion, gynaecological capsules containing either an oestradiol diether (ICD: promestriene) or only the excipient were administered for 40 consecutive days.

At the end of the treatment, the FSH, LH, oestrone (E₁) and oestradiol (E₂) plasma levels were not found to be significantly different from the pre-therapeutic values.

These results suggest that promestriene acts on the vaginal mucosa, therefore not being converted back into the hormone from which it was derived. Also, in its dietheroxide form, promestriene is incapable of crossing the malpighian (vaginal or epidermal) epithelium and of reaching the general blood circulation.

This discrepancy between the local anti-atrophic effects and the inability to exert systemic oestrogen activities singles out promestriene and justifies its therapeutic use when hormonally active oestrogens are contra-indicated, as in patients who have an oestrogen-sensitive cancer in their medical history.     

Effect of an intranasal LHRH agonist on gonadotrophins and hot flushes in post-menopausal women

Alterations in circulating gonadotrophins have been reported at the time of onset of menopausal flushes. In order to study this association D-SER(TBU)6-EA10-LHRH, a luteinizing hormone releasing hormone (LHRH) agonist was given intranasally at a dose of 200 micrograms twice daily to 12 post-menopausal women to study its effect on gonadotrophin secretion and hot flushes. Following an initial period of 3-5 days of increased gonadotrophin secretion, pituitary desensitization occurred, with a significant suppression of circulating LH and follicle-stimulating hormone (FSH) levels (P less than 0.001) and a reduction in gonadotrophin pulse amplitude (P less than 0.05). This was accompanied by a significant diminution of the pituitary's response to exogenous LHRH (P less than 0.05). However, no significant alteration in the incidence of hot flushes was observed on such therapy.     

Secretion of testicular steroids and gonadotrophins in hypothyroidism

Inconsistent alterations in gonadal steroidogenesis and pituitary functions have been reported in hypothyroid males. We have compared the lipid and endocrine profiles of the euthyroid and hypothyroid [thyroid-stimulating hormone (TSH) >100 mIU l(-1)] males. Hypothyroidism was found to be associated with an increase in the circulating level of total cholesterol and LDL-cholesterol (LDL-C) and a reduction in the levels of progesterone and testosterone, without any change in the serum levels of oestradiol and gonadotrophins. The failure of gonadotrophins to rise could be accounted by a normal level of serum oestradiol in the hypothyroid male. A mild hyperprolactinaemia was also noted in the hypothyroid patients. The reduction in serum testosterone level could be explained by (i) a reduced uptake of LDL-C by the Leydig cells and thereby a reduction in the synthesis of progesterone and consequentially testosterone, (ii) a further reduction in the rate of conversion of progesterone to testosterone, (iii) a higher rate of conversion of testosterone to oestradiol, (iv) a decrease in serum triiodothyronine and (v) hyperprolactinaemia. Rise in TSH needs to be investigated as a cause of the suppression of gonadal steroidogenesis.     

Defective Growth Hormone (GH) secretion and short-term treatment in Noonan syndrome

Auxological and endocrine data from 12 prepubertal children (3 males, 9 females) with Noonan syndrome (NS) were compared with those of 15 children with constitutional short stature (CSS), 20 children with partial GH deficiency (GHD), and 6 children with Turner syndrome (TS). Four children With NS were treated with human growth hormone (hGH) (n=4) (25 units/m² week, divided on daily s.c. doses). In children with NS, the peak serum GH response to clonidine (5.4 ± 2.7 ug/L) and glucagon (7.4 ± 3.4 ug/L) were significantly lower than those for children with CSS (14.8 ±3.4 and 12.8 ± 2.8 ug/L respectively). Nine out of the 12 (75%) children with NS did not mount normal GH peak (10 ug/L or more) after provocation. The 12-h integrated GH secretion in the 3 children With NS who had normal GH response to provocation (2.7 ± 0.7 ug/L) was markedly lower compared to that for children with CSS (6.7 ±1.2 ug/L). The serum insulin-like growth factor-1 (IGF-l) concentrations were lower in children with NS (67 ± 32 ng/ml) vs CSS (165 ±35 ng/ml), but not different from those for GHD children (59 ± 33 ng/ml). In 4 children with NS, hGH therapy for a year increased height growth velocity from 4.1 ± 0.3 cm/yr to 7.4 ±0.6 cm/yr and height standard deviation score (Ht SDS) from -2.2 ± 0.6 to -1.45 ±0.3. This growth acceleration was accompanied by an increase in IGF-I concentration (from 52 ±21 ng/ml to 89 ± 25 ng/ml). In summary, these results prove a defect of the GH secretion in children with NS and suggest that GH therapy has an important role in the management of their short stature.     

The hormone pattern in a case of arrhenoblastoma

A case of ovarian arrhenoblastoma in a 14-year-old girl is reported. The patient presented with primary amenorrhea, severe diffuse hirsutism, moderate clitorial enlargement and slight decrease in breast size. Hormonal examinations revealed high plasma testosterone and androstenedione levels, normal plasma prolactin, dehydroepiandrosterone-sulphate, 17-alpha-hydroxyprogesterone, urinary 17 ketosteroids and pregnanetriol and low plasma 17 beta oestradiol, oestrone, FSH and LH.Androgen concentrations decreased under dexamethasone suppression test. Following tumour ablation menses occurred spontaneously and normal hormone patterns were observed.     

Auswirkungen einer langdauernden exogenen Gonadotropinzufuhr auf die testikuläre Insuffizienz bei Dauerdialysepatienten

Zusammenfassung 13 männliche Dialysepatienten im Alter von 25–65 Jahren erhielten Gonadotropine (HCG-Primogonly®) zunächst 2 × wöchentlich 2000 IE und nach einer 2–3-wöchigen Therapiepause 1 × wöchentlich 2000 IE. Vor HCG und während der 4monatigen Behandlung wurden in 1- bis 2wöchentlichen Abständen Testosteron-, Dihydrotestosteron-, Androstan-Diol-, LH- und FSH-Spiegel radioimmunologisch bestimmt. Vor HCG-Zufuhr waren die Testosteronspiegel stark erniedrigt, die Testosteronmetaboliten (DHT und A-Diol) sowie die Gonadotropine (FSH und LH) im Plasma erhöht. Nach HCG kam es zu einem verzögerten und inadäquaten Anstieg der Testosteronspiegel auf Normalwerte. In der Therapiepause fielen die Werte sofort auf die Ausgangswerte ab. Mit einer reduzierten Dosis (2. Therapiephase) war es nicht möglich, eine anhaltende Erhöhung der Testosteronspiegel zu erzielen. DHT und A-DIol waren vor der HCG-Zufuhr erhöht und zeigten unter HCG — von einzelnen Ausnahmen abgesehen — keinen signifikanten Anstieg. Die Messung der LH-Spiegel ergab stark erhöhte Werte während der ersten Therapiephase. In der Therapiepause, während der 2. Therapiephase und am Ende der Behandlung lagen die LH-Konzentrationen wieder in Höhe der Ausgangswerte. Das Absinken der FSH-Spiegel während der HCG-Zufuhr wird auf den hemmenden Einfluß der ansteigenden Testosteronspiegel zurückgeführt.Unter der HCG-Zufuhr zeigten Körpergewicht, Serumeiweißspiegel, Hämoglobin und Hämatokrit keinen signifikanten Anstieg im Vergleich zu den vorher erhobenen Befunden. Ebenso war eine Besserung der bei 8 Patienten nachgewiesenen schweren Fertilitätsstörungen nicht festzustellen.Die erhobenen Befunde sprechen dafür, daß bei Patienten mit chronischer Niereninsuffizienz eine schwere urämisch-toxische Schädigung des Leydigzell-Systems vorliegt, die durch die Dauerdialysebehandlung nicht beseitigt wird. Der im Vergleich zu den stark erniedrigten Testosteronspiegeln inadäquate Anstieg der Gonadotropine erklärt sich möglicherweise durch einen negativen feed-back-Effekt der Testosteronmetaboliten. Die erhöht gefundenen Werte dieser Abbauprodukte kommen wahrscheinlich durch Akkumulation bei gestörter Nierenfunktion zustande.Mit dankenswerter Unterstützung der Firma Schering, Berlin, unter technischer Mitarbeit von Fräulein A. Berens