J Int Med Res (1978) 6,41

An Open Assessment ora New Low Dose Oestrogen Combined Oral Contraceptive Ivor Hughes, MB, ehB, General Practitioner, Liverpool, England

This was a multicentre general practitioner study using a new low dose oral contraceptive, Ovamin 30 (ethinyloestradiol 30 ug, ethynodiol diacetate 2 mg). Results showed a pregnancy rate calculated as a Pearl Index 0/0·4. A n analysis 0/ bleeding patterns showed consistently acceptable cycle control. From these results it would appear that Ovamin 30 is an effective and well tolerated low dose oral contraceptive preparation.

Introduction

Since 1969 evidence has accumulated which suggests that reduction of oestrogen content in combined oral contraceptives is of benefit. The evidence available at present suggests that a reduction in oestrogen content from 100 to 50 IJg is associated with a decrease in various side-effects related to oestrogen content, most notably thrombo-embolism (Inman et al 1970). Although there is no evidence to suggest that a reduction of oestrogen content from 50 to 30 IJg is associated with still fewer sideeffects, it is not entirely illogical to assume that this may be the case. In view of this the Family Planning Association decided in mid-1977 to regard oral contraceptives containing less than 50 IJg of synthetic oestrogen as 'preferred'. Ovamin 30 is an oral contraceptive containing 30 IJg of ethinyloestradiol and 2 mg of ethynodiol diacetate. This paper describes experience gained in evaluating the product for efficacy and acceptability in a group of women requesting oral contraception from their general practitioner. Materials and Methods

Both patients new to oral contraception and

those switching from other preparations for medical reasons were accepted for inclusion. Patients with recognized contra-indications to oral contraceptive therapy were excluded from the study. The nature of the study was explained to the patients participating in the investigation. This was a multicentre trial involving fifteen general practitioners who between them recruited a total of 504 patients, of whom 453 supplied at least one follow-up visit. Information on a total of 3236 women months of use has been amassed. The women recruited to the study were aged between sixteen and forty years. Individual total usage ranged from two to eighteen months. On admission to the study a history was taken and full examination (including pelvic examination and cervical smear) was performed. The patients were then issued with a month's supply of tablets and a diary card for the recording of tablet taking and vaginal bleeding pattern. At follow-up a new diary card and a fresh supply of tablets were issued on a monthly basis. The patients recruited to the study were exposed to pregnancy throughout the duration of the study. At each subsequent visit an attempt was made to elicit

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7

5

9

Lost to follow-up

8

1

3

1

1

2

3

1

I

Voluntary pregnancy

Involuntary pregnancy

Raised blood pressure

Leg pains

Cervical erosion

Breast discomfort/weight gain

2

1

Depression/headaches

2

3

1

I

296

5

Amenorrhea 3

335

4

6

1

381

3

Excessive/irregular bleeding

3

425

453

Number of patients

Reasonfor discontinuing

2

1

Pack (28 days)

2

2

1

1

257

6

3

1

I

1

207

7

5

1

1

2

1

160

8

3

1

1

114

9

2

91

10

I

6

85

11

I

78

12

70

13

I

I

67

14

1

61

15

Showing the number of patients receiving treatment in each 28 days ofthe trial, the number who withdrew and the stage at which they did so

Table 1

59

16

2

1

56

17

I

41

18

Total

58

12

1

1

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withdrawals

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I Hughes

43

symptoms experienced by patients in an objective manner. Leading questions regarding symptomatology were avoided. The preparation was provided in packs of 2'1 tablets, the first tablet being taken on Day 5 of the initial menstruation in the usual manner. Results Of the 504 patients recruited a total of forty-one patients was followed for up to eighteen months. All tabulations apply to data gained up to and including the eighteenth month of use. The data are based on the 3236 completed cycles. Table 1 gives information about side-effects as related to the number of the pack in which they occurred. It will be seen that thirty-nine patients withdrew from the study because of side-effects which could reasonably be ascribed to the preparation and only eighteen of these were due to some type of menstrual disorder. Twelve patients withdrew from the trial in order to conceive. There was one involuntary pregnancy and fifty-eight patients were lost to follow-up.

The characterization of episodes of bleeding into menstrual or intermenstrual groups is exceedingly difficult (Rowe et al 1974). Bleeding patterns were thus analyzed using a method based on arbitrary time intervals of 100 days as described by Rowe et al (1974), Rodriguez et al (1976) and as' used by Postlethwaite (1976). Using this method, a total of 125 patients have supplied data on at least 100 days of use and, during this first 100 days, patients bled or spotted, on average, a total of 15·4 days (s.d. 7·3 days). This bleeding occurred in 3·4 day, (s.d, 1·4 days) distinct episodes, with bleedingfree intervals of mean length 23 days (s.d, 13·7 days). Subsequent blocks of 100 days continue this pattern with episodes of bleeding/spotting of mean length of 4 days separated by bleeding-free intervals of 23 days. Figures 1-4 demonstrate the early establishment of an acceptable bleeding pattern which is maintained in later cycles. The pregnancy rate for this preparation, calculated by the Pearl Index, is 0·4 per 100 woman years with 95% confidence limits of 0·01 to 2·24.

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Fig I Mean number ofbleedingepisodesin consecutive 100 day intervals during use ofOvamin 300

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44

The Journal ofInternational Medical Research 25 24 23 22 21 20

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Fig 2 Mean length ofbleeding-freeintervals (in days) in consecutive 100 day segments ofuse ofOvamin 30.

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Fig 3 Mean length ojbleeding episodes (in days) during consecutive 100 day intervals during use ojOvamin 30.

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45

I Hughes

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0 0

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Fig 4 Mean number ofdays ofbleeding per 100 days in consecutive 100 day intervals during use ofOvamin 30.

Discussion Ovamin 30 contains 30 pg of ethinyloestradiol and 2 mg of ethynodiol diacetate. These features ensure that it has the lowest possible dose of oestrogen together with sufficient progestogen to enable an acceptable bleeding pattern to be produced and maintained. All 30 pg oestrogen-containing oral contraceptives have as their aim the reduction of side-effects related to this compound. These include thrombo-embolic disease, disturbances of carbohydrate and fat metabolism, alteration of various blood clotting factors, occasional liver disturbances, etc. Although no evidence is yet available, studies are in progress to determine whether the above effects are reduced with 30 pg products as opposed to those products containing 50 pg of oestrogen. Ovamin 30 appears to be an effective and well tolerated low oestrogen contraceptive. I am grateful to the following for their cooperation in allowing me to use information obtained from patients under their care: E Harris, J Collinson, N Cannon, J Todd,

D Jennings, P Caller, P F Cameron, N H Brodie, J Lissenden, R McGhie, A Smith, and I should like to thank Mrs P Hessian of the Medical Department, Searle Laboratories for help and advice with the statistics.

REFERENCES Inman W H W, Vessey M P, Barbro Westherholm & England A (1970) Thrombo-embolic disease and the steroidal content of oral contraceptives. A report to the Committee of Safety of Drugs. British Medical Journal 2,203 Postlethwaite D L (1976) Evaluation of an oral contraceptive containing only progestogen. Practitioner 217, 439 Rodriguez G, Faundes-Latham A & Atkinson L E (1976) An approach to the analysis of menstrual patterns in the critical evaluation of contraceptives. Studies in Family Planning 7, 42 Rowe P J etal (1974) Comparative bleeding patterns of a progesteronereleasing IUD. Analysis of intra-uterine contraception. In: Proceedings ofthe Third International Conference on Intrauterine Contraception, Cairo. Ed by F Hefnawi and S J Segal, p 185. North Holland, Amsterdam

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