81

significantly higher than the after-MPA mean of 56.3225.1 MIU/ml (p (0.02). The

FSH mean before MPA was 88.3+18.55 MIU/ml and the after-MPA mean was higher at

q6.6z31.2 MIU/ml. This invites speculation, but is not significant.

The mean plasma level of E2 before the g-week course of treatment was

36.5225.9 and afterwards it was 25.4+14.37, which is suggestively but not

significantly lower (p (0.08).

The use of MPA in post-menopausal patients thus results in a significant

improvement in climacteric symptoms, but the mechanism of action is still

unclear, there being a decrease in the plasma level of LH, an increase in FSH

and a downward trend in E2. We would speculate that MPA exerts an effect on the

hypothalamic neurotransmitter involved in the genesis of climacteric symptoms,

but this is unlikely to be through the metabolism of MPA to oestrogen.

4 PLASMAD-ENDORPHIN IN POST-MENOPAUSAL WOMEN

Fatma A. Aleem and Tracy K. McIntosh - Valhalla, New York, U.S.A.

Several recent studies indirectly suggest that endogenous opioids,

specifically Aendorphin (b-EP), play a role in the genesis of menopausal hot

flushes through effects on the hypothalamic thermoregulatory centre. An accurate

assessment of&EP's role in the aethiology of hot flushes clearly required

direct measurement of &-EP by means of a highly specific and accurate

radioimmunoassay (RIA) method. Once we had developed a specific RIA, using

anti 4 -1ipotrophin (A-LPH) antibodies to eliminate the&LPH from the specimen

and high performance liquid chromatography to purify the&EP, we were able to

complete the study. Its purpose was threefold: 1) to determine&EP levels in

post-menopausal women and to compare them with those in normally menstruating

controls, 2) to examine the acute effects of oophorectomy on&EP levels, and 3)

to investigate changes in M 2 SD of&-EP with the clinical onset of hot flushes.

The &EP level in 13 post-menopausal women (7 surgical and 6 natural ??enopauses) was found to be 48.6~13.8 pglml, which was significantly lower than the M 2 SD

in 10 normally menstruating controls (P- <0.005).

Levels of BEP were measured 5 days after bilateral oophorectomy in 3

pre-menopausal women and revealed an average fall of 41% from the pre-operative

plasma level. The level offi-EP rose immediately after hot flushes in 4

82

post-menopausal women and was found to be significantly elevated over baseline

levels (P=O.O2).

Our data showed a lower basal level of&EP in post-menopausal women and also

suggest that &-EP may play a direct or indirect role in the genesis of

menopausal hot flushes.

5 ROLE OF MELATONIN IN THE REGULATION OF THE HYPOTHALAMIC PITUITARY AXIS

DURING THE MENOPAUSE

Fatma A. Aleem, Uzi Weinberg and Eliot Weitzman - Valhalla, New York,

U.S.A.

The large volume of literature suggesting that melatonin is involved in the

regulation of the hypothalamic pituitary-gonadal axis prompted our study to

establish its possible role in the regulation of this axis during the menopause.

The effect of a continuous intravenous (IV) infusion of melatonin (5-methoxy

N-acetyl tryptamine) on plasma concentrations of luteinizing hormone (LH) was

studied in three post-menopausal women. Melatonin was infused IV (125 mg/hr) for

48 hours, prior to which the 24-hour basal LH pattern was determined in each

subject as a control. Pharmacological concentrations of serum melatonin were

maintained throughout the infusion. The melatonin infusion produced a dramatic

suppression of serum LH concentrations to below baseline levels in all three

women (LH suppression percentages were 58.03 %, 57.74 % and 54.66 %

respectively). These findings indicate that melatonin may play a possible

modulatory role in regard to the hypothalamic pituitary axis during the

menopause. This study is part of an investigation to examine the possible role

of this neurotransmitter's involvement in the pathophysiology of vasomotor

symptoms.

Day 1 Day 2 Day 3 Suppression Subject No Melatonin Melatonin Melatonin of LH

1 59.4210.6 41.7~12.5 23.4211.5 58.03%

2 65.3212.9 49.5+15.8 27.6512.0 57.74%

3 58.2+10.0 42.5* 6.3 26.42 5.9 54.66%