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to its previous slackness. In the second half of each cycle and for some days after
some of the women had sore erect nipples and vein engorgement.
At the beginning all the women complained of miscellaneous symptoms in varying
degree, such as fatigue, giddiness, headache, palpitation, muscle weakness, arthralgia,
poor concentration, failing memory, abnormal micturition, and general malaise. At the
end of the first cycle there were only two complaints. At the beginning of the second
cycle some complaints had appeared again and continued to the end of the trial. Seven
women were enthusiastic over an improved sense of well-being at the end of the first
cycle; but this number fell to two by the end of the second cycle. It is possible that the
effect of the tablets, or the excitement of taking part in the trial, or the stimulation
given by the enthusiasm of the staff, or the expectation of improved health, or any of
these factors in combination might have accounted for the feeling of well-being at the
end of the first cycle. But during the second cycle, as the women realized they had to
endure some discomfort and inconvenience, the enthusiasm probably waned; or it is
possible the medication was not so effective.
At the beginning of the trial nine women complained of hot flushes. At the end
of the first cycle these had all disappeared. At the beginning two women complained
of heavy nocturnal drenching sweats with feelings of coldness and weakness afterwards.
These disappeared by the end of the first cycle and did not recur. Three women complained
of spasms of the calf muscles at the end of the first cycle and one woman
complained in the second cycle. We have noticed this not infrequently with steroid
medication. Details of various emotions were given by most of the women at the
beginning, practically all of which disappeared by the end of the first cycle. This
improvement declined during the two cycles and was only partially restored during the
second cycle. By the end of the trial the emotional situation seemed to be no better
than when we started.
Menstruation occurred at the end of each cycle with all the women except two
who had had hysterectomy. It was prolonged in some instances. At the end of the
first cycle three women went on for 7 days and one for 13 days. At the end of the
second cycle one went on for 7 days, one for 9, and one for 11 days. This is clearly
undesirable, being much too long and too heavy. It possibly had an adverse effect on
the health of the women in the second cycle and afterwards.
We observed the changes in the genital tract both clinically and by cytology. All
the women had a heavy vaginal secretion under the influence of oestrogen. It dried
up quickly when the tablets were stopped. Midway through the second cycle four
women showed swelling and purple discoloration of the cervix, which subsided two
weeks after ceasing taking tablets : very likely a progesterone effect. Smears for cytology
were taken at every visit and were examined for oestrogen, progestogen, and androgen.
At the middle of the first cycle there was an enormous oestrogen response which fell
slightly towards the end; between the cycles the oestrogen fell markedly; it was again
enormously increased by the middle of the second cycle, and fell again slightly towards
the end. After the final two weeks the oestrogen was back again to its initial level at
the start of the trial. The progestogen showed a marked increase at the end of the first
cycle; it fell back again between the cycles but was high again at the end of the second
cycle. It had fallen to its original level at the end of the trial. The androgens tended
to fall in the middle of each cycle but the figures are not very convincing. The great
influence of oestrogen and progestogen on the genital tract was very apparent. During
each cycle some of the women had side-effects such as headache, bloated feeling, and
breast discomfort.
The most remarkable finding was the manner in which the serum cholesterol level
fell from the beginning to the end of the first cycle (A to C); then it rose at the
beginning of the second cycle and fell again at the end (D to F); and then it rose again
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