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The effect of norethindrone-mestranol on cervical mucus
The effect of norethindrone-mestranol
on
cervical mucus JAMES
A.
Cleveland,
Ohio
BOWMAN,
JR.,
M.D.
Measurements of spinnbarkheit and amount and viscosity of cervical mucus were made on 15 healthy parous women at midcycle and following the administration of 1 mg. norethindrone and 0.05 mg. mestranol. It was demonstrated that spinnbarkheit was greatly reduced and that the cervical mucus was decreased in amount and viscosity. Measurement of s#innbarkheit is a simple test which could be used to test the antifertility effect of the combination-type oral contraceptives.
THERE HAVE been many reports and reviews relating to the mode of action of the oral contraceptives since Gregory Pincusl first published his studiesin 1955. In spite of the impressive growth in the literature relative to the mechanism of action by which fertility is inhibited, our present knowledge is still empiricaL Adding to the difficulty is the lack of knowledge of the various hormonal parameters of the so-called “normal” menstrual cycle. At the present time there is no definition of the lowest urinary pregnanediol value which is compatible with ovulation and normal luteal function.3 This suggeststhat the urinary pregnanediol studies may not always be indicative of failure of ovulation. Cohen and Perez-Pelaez4 suggest that the outpouring of cervical mucus and spinnbarkheit-be used as a test of ovulation. In studies done with low dosage continuous oral progestins, with a high percentage of ovulatory cycles, the antifertility mechanism appeared to be closely related to cervical mucus changes rather than to any endometria1 effect. The cervical mucus is more sensitive than the endometrium to low-dosageprogestins6 During the fertile phase of the cycle, on days 13 and 14 of a 28 day cycle, the cervical mucus is thin, profuse, clear, and easy to From the Department of Obstetrics and Gynecology, The School of Medicine, Case-Western Reserve University. Norinyl was provided through the courtesy of the Syntex Laboratories.
aspirate. The length of spinnbarkheit formation may be 10 cm. or more. It is favorable to sperm survival, and pus cells are normally absent. During other phasesin the cycle, the mucus is thick, scant, turbid, and difficult to aspirate. Spinnbarkheit formation may be as long as 1 cm. It is unfavorable for sperm survival, and pus cells are generally present. Progestins of the 19-nor steroid group produce cervical mucus alterations which in themselves provide effective means of conception control. With lower dosageoral contraceptives, this added protection may be of since “breakconsiderable importance, through ovulation” has been reported to occur in somecases.6r ’ The purpose of this report is to present alterations in the spinnbarkheit test in a group of women during normal menstrual cycles and cycles in which oral progestins were administered. The spinnbarkheit test is a simple and practical test for determining the viscosity of cervical mucus.I Material
and
methods
Fifteen healthy, fertile, parous women without evidence of pelvic abnormality were selected for the study. The women ranged from 22 to 33 years of age. A spinnbarkheit measurement and an estimate of quantity and viscosity of cervical mucus were made in each woman at midcycle prior to treatment. On two subsequent cycles norethindrone 1 mg. and mestranol 0.05 mg. (Norinyl- 1) were given in a single daily dose 1039
1040
December 1, 1968 Am. J. Obst. & Gynec.
Bowman
Table I. Alterations and two subsequent
in cervical mucus in 15 women during a normal control cycles while under treatment with norethindrone-mestranol Average
Case No.
Age
1 2 3 4 5 F 8 9 10 11 12 13 14 15
25 28 26 31 26 22 28 33 29 32 24 23 22 25 28
Spinnbarkheit
normal
Viscosity
12 9 9 9.5 10 12 12 9 3 9 10 3 9 13 8
First Spinnbarkheit
Quantity
+++
Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin
orally for 20 consecutive days of each menstrual cycle commencing on the fifth day after the onset of menses, and the examinations of the mucus were repeated. Results
and
comment
The results are tabulated in Table I. During the untreated cycle 86 per cent of the women had a large amount of thin mucus with spinnbarkheit greater than 8 cm. at midcycle. In the untreated normal cycles the range of spinnbarkheit was 3 to 13 cm. with a mean value of 9 cm. The mucus was thin in all cases. Two patients had spinnbarkheit of 3 cm. The measurements were made at the fourteenth cycle day following the first normal menses after childbirth. These 2 patients may have had early ovulation. Following the administration of the oral combination of norethindrone and mestra-
Second
’ Viscosity Thick Thick Thick Thick Thin Thick Thick Thick Thick Thick Thick Thick Thick Thick Thick
0.5 1.0 0.5 2.0 3.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.8 2.0
+++ +++ +++ +c ++ +++ +++ +++ i++ t++ ++ it+ ++++ +++
cycle
cycle
Quantity
+ $ + + +i+ + + + ++ + + 4-t + +++
Spinnbarkheit 1.0 2.5 0.4 2.5 2.5 1.0 0.3 0.5 1.0 2.0 1.0 0.3 1.5 0.5 1.0
cycle
Viscosity Thick Thick Thick Thick Thin Thick Thick Thick Thick Thick Thick Thick Thick Thick Thick
Quantity
+ f ++ f 4-f + + ++ ++ ++ + + ++ +
nol, 93 per cent of the women had a small amount of thick mucus with a spinnbarkheit of 2 cm. or less during the first treatment cycle. In the second treatment cycle the spinnbarkheit was 2 cm. or less in 80 per cent of the women. During the treatment cycles the range of spinnbarkheit was 0.3 cm. to 3.0 cm., with a mean value of 1.2 cm. One patient continued to have mucus of thin viscosity during the three observations, but the spinnbarkheit measurement decreased from 10 cm. to 2.5 cm. at the third cycle. It would appear that norethindrone in low dosage can produce the characteristic progesterone-dominated cervical mucus which is hostile to sperm penetration. These changes may contribute to the contraceptive efficiency of combination progestins such as norethindrone and mestranol.
REFERENCES
1.
2. 3.
4.
Pincus, G.: Proc. ference on Planned pp. 175-185. Diczfalusy, E.: AM. 136, 1968. Gual, C., Becerra, Goldzhieher, J. W.: 97: 443, 1967. Cohen, M. R., and Steril. 16: 158, 1965.
Fifth International Parenthood, Tokyo, J. OBST. C., AM.
&
GYNEC.
Rice-Wray, J. OBST.
Perez-Pelaez,
Con1955,
M.:
E., &
5.
100:
6. 7.
and
8.
Martinez-Manautou, and Rude& H.: Moghissi, K.: Goldzieher, J. T.: J. A. M. A. Cohen, M. R.:
J., Giner-Velasquez, J., Fertil. & Steril. 18: 57, 1967. Fertil. & Steril. 17: 663, 1966. W., Moses, L. E., and Ellis, L. 180: 359, 1962. Fertil. & Steril. 3: 201, 1952.
GYNEC.
Fertil.
&
IO515 Carnegie Cleveland, Ohio
Avenue 44106
on
cervical mucus JAMES
A.
Cleveland,
Ohio
BOWMAN,
JR.,
M.D.
Measurements of spinnbarkheit and amount and viscosity of cervical mucus were made on 15 healthy parous women at midcycle and following the administration of 1 mg. norethindrone and 0.05 mg. mestranol. It was demonstrated that spinnbarkheit was greatly reduced and that the cervical mucus was decreased in amount and viscosity. Measurement of s#innbarkheit is a simple test which could be used to test the antifertility effect of the combination-type oral contraceptives.
THERE HAVE been many reports and reviews relating to the mode of action of the oral contraceptives since Gregory Pincusl first published his studiesin 1955. In spite of the impressive growth in the literature relative to the mechanism of action by which fertility is inhibited, our present knowledge is still empiricaL Adding to the difficulty is the lack of knowledge of the various hormonal parameters of the so-called “normal” menstrual cycle. At the present time there is no definition of the lowest urinary pregnanediol value which is compatible with ovulation and normal luteal function.3 This suggeststhat the urinary pregnanediol studies may not always be indicative of failure of ovulation. Cohen and Perez-Pelaez4 suggest that the outpouring of cervical mucus and spinnbarkheit-be used as a test of ovulation. In studies done with low dosage continuous oral progestins, with a high percentage of ovulatory cycles, the antifertility mechanism appeared to be closely related to cervical mucus changes rather than to any endometria1 effect. The cervical mucus is more sensitive than the endometrium to low-dosageprogestins6 During the fertile phase of the cycle, on days 13 and 14 of a 28 day cycle, the cervical mucus is thin, profuse, clear, and easy to From the Department of Obstetrics and Gynecology, The School of Medicine, Case-Western Reserve University. Norinyl was provided through the courtesy of the Syntex Laboratories.
aspirate. The length of spinnbarkheit formation may be 10 cm. or more. It is favorable to sperm survival, and pus cells are normally absent. During other phasesin the cycle, the mucus is thick, scant, turbid, and difficult to aspirate. Spinnbarkheit formation may be as long as 1 cm. It is unfavorable for sperm survival, and pus cells are generally present. Progestins of the 19-nor steroid group produce cervical mucus alterations which in themselves provide effective means of conception control. With lower dosageoral contraceptives, this added protection may be of since “breakconsiderable importance, through ovulation” has been reported to occur in somecases.6r ’ The purpose of this report is to present alterations in the spinnbarkheit test in a group of women during normal menstrual cycles and cycles in which oral progestins were administered. The spinnbarkheit test is a simple and practical test for determining the viscosity of cervical mucus.I Material
and
methods
Fifteen healthy, fertile, parous women without evidence of pelvic abnormality were selected for the study. The women ranged from 22 to 33 years of age. A spinnbarkheit measurement and an estimate of quantity and viscosity of cervical mucus were made in each woman at midcycle prior to treatment. On two subsequent cycles norethindrone 1 mg. and mestranol 0.05 mg. (Norinyl- 1) were given in a single daily dose 1039
1040
December 1, 1968 Am. J. Obst. & Gynec.
Bowman
Table I. Alterations and two subsequent
in cervical mucus in 15 women during a normal control cycles while under treatment with norethindrone-mestranol Average
Case No.
Age
1 2 3 4 5 F 8 9 10 11 12 13 14 15
25 28 26 31 26 22 28 33 29 32 24 23 22 25 28
Spinnbarkheit
normal
Viscosity
12 9 9 9.5 10 12 12 9 3 9 10 3 9 13 8
First Spinnbarkheit
Quantity
+++
Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin Thin
orally for 20 consecutive days of each menstrual cycle commencing on the fifth day after the onset of menses, and the examinations of the mucus were repeated. Results
and
comment
The results are tabulated in Table I. During the untreated cycle 86 per cent of the women had a large amount of thin mucus with spinnbarkheit greater than 8 cm. at midcycle. In the untreated normal cycles the range of spinnbarkheit was 3 to 13 cm. with a mean value of 9 cm. The mucus was thin in all cases. Two patients had spinnbarkheit of 3 cm. The measurements were made at the fourteenth cycle day following the first normal menses after childbirth. These 2 patients may have had early ovulation. Following the administration of the oral combination of norethindrone and mestra-
Second
’ Viscosity Thick Thick Thick Thick Thin Thick Thick Thick Thick Thick Thick Thick Thick Thick Thick
0.5 1.0 0.5 2.0 3.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 1.0 0.8 2.0
+++ +++ +++ +c ++ +++ +++ +++ i++ t++ ++ it+ ++++ +++
cycle
cycle
Quantity
+ $ + + +i+ + + + ++ + + 4-t + +++
Spinnbarkheit 1.0 2.5 0.4 2.5 2.5 1.0 0.3 0.5 1.0 2.0 1.0 0.3 1.5 0.5 1.0
cycle
Viscosity Thick Thick Thick Thick Thin Thick Thick Thick Thick Thick Thick Thick Thick Thick Thick
Quantity
+ f ++ f 4-f + + ++ ++ ++ + + ++ +
nol, 93 per cent of the women had a small amount of thick mucus with a spinnbarkheit of 2 cm. or less during the first treatment cycle. In the second treatment cycle the spinnbarkheit was 2 cm. or less in 80 per cent of the women. During the treatment cycles the range of spinnbarkheit was 0.3 cm. to 3.0 cm., with a mean value of 1.2 cm. One patient continued to have mucus of thin viscosity during the three observations, but the spinnbarkheit measurement decreased from 10 cm. to 2.5 cm. at the third cycle. It would appear that norethindrone in low dosage can produce the characteristic progesterone-dominated cervical mucus which is hostile to sperm penetration. These changes may contribute to the contraceptive efficiency of combination progestins such as norethindrone and mestranol.
REFERENCES
1.
2. 3.
4.
Pincus, G.: Proc. ference on Planned pp. 175-185. Diczfalusy, E.: AM. 136, 1968. Gual, C., Becerra, Goldzhieher, J. W.: 97: 443, 1967. Cohen, M. R., and Steril. 16: 158, 1965.
Fifth International Parenthood, Tokyo, J. OBST. C., AM.
&
GYNEC.
Rice-Wray, J. OBST.
Perez-Pelaez,
Con1955,
M.:
E., &
5.
100:
6. 7.
and
8.
Martinez-Manautou, and Rude& H.: Moghissi, K.: Goldzieher, J. T.: J. A. M. A. Cohen, M. R.:
J., Giner-Velasquez, J., Fertil. & Steril. 18: 57, 1967. Fertil. & Steril. 17: 663, 1966. W., Moses, L. E., and Ellis, L. 180: 359, 1962. Fertil. & Steril. 3: 201, 1952.
GYNEC.
Fertil.
&
IO515 Carnegie Cleveland, Ohio
Avenue 44106