A u s t . N.Z.J. Obstet. Gynaec.
(1961) 1 : 73
Dimethisterone in Dysfunctional Uterine Bleeding
G. C . Liggins
T h e Postgraduate School of Obstetrics and Ggnaecology,
National Women’s Hospital, Auckland
T H E use of oral progestational agents in
the management of dysfunctional uterine
bleeding is now well established. A number
of reports describe good results following the
use of nor-ethisterone and nor-ethisterone
acetate (Boschann, 1958; B i s h o p and
Almeida, 1960; ,Taymor and Sturgis, 1960) ;
Enavid (Chalmers, 1959; Southam, 1958) ;
17-a-hydroxyprogesterone capronate (Gold
and Cohen, 1958) and various other pro-
gestational agents. Reports on the use of
dimethisterone have so far been limited to
the treatment of secondary amenorrhoea
(Matthew, 1959) and premenstrual tension
(Dalton, 1959; Appleby, 1960). This paper
describes the results obtained with dimethis-
terone in the treatment of a selected group of
patients suffering from dysfunctional uterine
bleeding.
TABLE 1
Material
Total Number of Patients Treated
65
A g e Distribution
Under 21 8
21-30 12
31-40 15
Over 40 30
N u m b e r of Previous Curettages
None 12
1 36
2 8
3 8
>3 1 oestradiol daily throughout the cycle.
Material and Methods
The material consists of 65 patients re-
ferred by consultants of the National
Women’s Hospital. Eighty-two per cent. of
these patients had been curetted on at least
one occasion previously (Table I), and re-
sponse had either been absent or short-lived.
Organic pathology was excluded in all
patients except adolescents by examination
under anaesthesia, dilatation of the cervix
and exploration of the uterine cavity. Hyster-
ography was performed in any case where
doubt remained. Other investigations included
white cell count, haemoglobin, platelet count
and bleeding and clotting times. Gross
thyroid disorder was excluded by history,
physical examination and serum cholesterol
determination. The glucose tolerance was esti-
mated in cases of endometrial hyperplasia
where obstetric or family histories were sug-
gestive.
The presence or absence of ovulation was
determined by premenstrual endometrial
biopsy, basal temperature charts, vaginal
cornification indices and the cervical ferning
phenomenon. Endometrial biopsy was avoided
in adolescents, reliance being placed on the
other tests.
Treatment was based on a scheme of cycli-
cal dosage providing a total of 150 mg. of
dimethisterone during 10 days from the 17th.
to the 26th. day of each cycle. Increased
dosage up to 300 mg. was used in those
patients responding unfavourably to the lower
dosage but no significant improvement in
response was noted. No oestrogen was used
unless there was definite evidence from the
vaginal smear of oestrogen deficiency. Oestro-
gen dosage was then 0.02 mg. of ethinyl
The progestational effects of dimethisterone
were studied by endometrial biopsy, cornifi-
cation indices and cervical ferning 7-10 days
after the start of the first course of treat-
ment.
74 AUST.AND N.Z. JOURNALOF OBSTETRICS
AND GYNAECOLOGY
Results
Thirty-six patients showed no evidence of
ovulation; in 22 ovulation was demonstrated;
and no diagnosis was made in the remaining
7 patients (Table 2 ) .
TABLE 2
Incidence of Ovulation
The preponderance of anovulatory cases is
thought to be due to the method of selection
of patients; cases of ovulatory dysfunctional
bleeding are in general less severe than cases
of anovulatory bleeding and respond better
to curettage, thus being less likely to be
referred for special investigation and treat-
ment. The histology of the endometrium in
the anovulatory group is summarized in
Table 3 . The incidence of endometrial hyper-
plasia and of normal non-secretory endo-
metrium was equal.
TABLE 3
Anovulatory Group
Histology of Endometrium
Hyperplastic endometrium 17
Normal non-secretory endometrium 17
Not determined 2 One of the failures, a patient aged 38
Suitably timed biopsy samples from 26
patients with anovulatory cycles were
examined for secretory response to dimethis-
terone. It will be seen that the relation of
dosage to response varies widely, the ex-
TABLE 4
Relationship of Endometrial Response to Dosage
n ‘Endometrial Development
Proliferative
Early secretory
Dose of Dimethisterone p e r Cycle (mg.)
75-100
4
1
Late secretory 0 1
tremes being no response to 420 mg. and
late secretory changes after 150 mg. (Table
4 ) . It was noted that endometrial changes
tended to be patchy, especially in endometria
with glandular hyperplasia. All stages of
glandular development from proliferative to
late secretory might be seen in one endo-
metrial biopsy sample. Secretory changes in-
duced by dimethisterone were usually indis-
tinguishable from those following ovulation.
In 3 cases stromal oedema was excessive and
stromal development was in advance of
glandular development.
Sixty-five patients were fully investigated
and treated with dimethisterone. Follow-up of
7 of these is not yet long enough to assess
the result of treatment. The response is
classed as good in 51 patients, poor in 5
and failed in 2 (Table 5 ) . A good response
includes those patients “cured” by spon-
taneous menopause or the spontaneous onset
of ovulation in adolescents and those in
whom symptoms could be adequately con-
trolled by courses of cyclical treatment. In
a poor result, response to treatment occurred
but insufficient to provide a satisfactory
measure of control.
When the results of treatment of the
anovulatory and ovulatory groups are con-
sidered separately, it is seen that the result
in every patient of the anovulatory group is
good, while in the ovulatory group the result
in 13 patients is good, in 4 patients is poor
and there are 2 failures (Table 6 ) .
years, was treated by hysterectomy. Macro-
scopic and microscopic examination of the
uterus showed no abnormality. The other
failure was subsequently tried with further
forms of conservative treatment. Her pro-
gress remains unsatisfactory but her symp-
toms do not warrant hysterectomy.
101-150
1
8
151-200
2
1
Over 200
2
2
3 1
’I
 G. C. LIGGIYS
Side-effects from dimethisterone were few.
Spasmodic dysmenorrhoea developed in 3
adolescents whose anovulatory cycles had
previously been painless. Although pain was
severe in 2 of these girls during the first
cycle of treatment, pain during subsequent
cycles diminished and in no case caused
incapacity or required abandonment of treat-
ment. Two patients complained of minor
headaches. There were no complaints of
nausea or vomiting.
TABLE 5
Results of Treatment
Good 51
Poor 5 been the difference in results obtained in the
Failed 2 anovulatory group and the ovulatory group.
Not yet known 7 In the former, where control depends on
TABLE 6
Results of Treatment
Ovulatory Anovulatory
Group Group
Good 13 33
Poor 4 0
2 0
Failed
Not yet known 3 3
Discussion
The factors responsible for the favourable
result obtained in this trial include spon-
taneous remission, careful investigation and
supervision, and the use of dimethisterone.
The relative importance of each of these
factors cannot be determined in this uncon-
trolled trial. The material consists largely of
patients whose symptoms had been present
for at least 12 months and who had failed to
respond to the usual conservative measures.
The spontaneous remission rate in such
material is likely to be low compared with
an unselected group.
The formidable difficulties confronting
trials of the relative potency of progesta-
tional agents have been pointed out by
Swyer (1959). It is clear that none of these
agents possesses all the properties of pro-
gesterone. Swyer found that the po'tency of
75
dimethisterone when measured by the post-
ponement of normal menstruation was ex-
tremely low. It is apparent, however, from
the present trial, that when measured by the
secretory transformation of oestrogen primed
endometrium, the potency of dimethisterone
is of the same order as progestational agents
such as nor-ethisterone and Enavid. This
inconsistency might be the result of differing
oestrogenic activities of these agents, di-
methisterone having minimal oestrogenic
effect, although Swyer did not find that added
oestrogen increased the ability of dimethis-
terone to postpone menstruation. The prac-
tical expression in the present trial of these
widely differing potencies of two of the pro-
gestational properties of dimethisterone has
secretory transformation and withdrawal
bleeding, all cases did well. In the latter
group, where control depends in part on pro-
longation of shortened cycles, results were
less reliable and break-through bleeding was
troublesome.
Summary
1. Sixty-five patients suffering from dysfunc-
tional uterine bleeding were treated with
dimethisterone.
2. Among 58 patients followed up for long
enough to determine the response to treat-
ment, the result was considered good
in 51.
3. Thirty-three cases of anovulatory bleed-
ing all responded well.
4. Among 19 cases of ovulatory bleeding, a
good result was obtained in 13, a poor
result in 4, and treatment failed in 2
patients.
5. No claim is made that these results de-
pend solely on the use of dimethisterone.
Nevertheless it would appear that most
cases of dysfunctional uterine bleeding
who do not respond to curettage can be
satisfactorily controlled and the need for
major surgical procedures avoided by
combining careful supervision with cycli-
cal administration of dimethisterone.
76 AUST.AND N.Z. JOURNAL OF
Acknowledgements
This study was made possible by a grant
to the University of Auckland by British Drug
Houses (New Zealand) Limited, who also
supplied dimethisterone (Secresteron) . The
author is indebted to Professor H. M. Carey
and the Senior Obstetrical and Gynaecological
Staff of the National Women’s Hospital for
their encouragement and co-operation.
References
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Although these cranial blood-swellings can-
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described, they have been frequently mistaken
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this collection of blood is usually beneath
the scalp and the tendinous aponeurosis of
the occipito-frontalis muscle, the bone being
covered by its pericranium.
OBSTETRICS
AND GYNAECOLOCY
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Great misapprehension has been entertained
by several authors respecting the progress of
these tumours; it has been stated that much
constitutional disturbance would be set up,
if this accumulation of blood, or bloody fluid,
were alIowed to remain; that it would become
putrid; that fever would result; that there
would be danger of ulceration, sloughing,
etc.; and hence it was recommended to open
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an early period, before the above-mentioned
changes had had time to take place. Mercurial
frictions have also been recommended, in
order to produce absorption. . . . It may
therefore very naturally be asked what is the
treatment of these tumours which Professor
Naegele practised with such uniform success,
and with which I have been equally for-
tunate? I would answer that it is of the
simplest kind - do nothing.
Edward Rigby. (Trans. Obstet. SOC.Lond.,
1860). From “Two Cases of Cranial Blood-
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