Blood pressure and oral progestational agents

Bhd

pressure and oral pmgestational

A prospective

W.

DALLAS

B.

BRENT

A.

ROBERT

M.D. DOIIGLAS,

M.C.H.

BLUMENSTEIN, A.

:ftlcintci.

study of 119 black women

HALL,

hlAR(;ARET

agents

p~3.D.

HATCHER.

M.D.,

M.P.H

Grorgicc

Blood pressure and body weight were carefully measured in 119 young black women before and after 6 to 24 months of contraceptive therapy with oral progestational agents (minipills). Results are compared with 673 women followed during continued use of nonhormonal contraceptive methods. Minipill therapy (0.35 mg of norethisterone) was associated with no significant (p > 0.05) increase in either systolic or diastolic blood pressure means. Minipill users did not develop diastolic blood pressures of 90 mm Hg or more during the study period. Substantial weight gain occurred as a side effect. (AM. J. OBSTET. GYNECOL. 136:344, 1980.)

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Volume Number

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those women that the standard cuff (23 by 13 cm bladder) did not adequately fit. Initial and repeat visit measurements were made in the same room and the conditions surrounding the blood pressure measurements have remained stable throughout the three year program. The data set includes 20,639 women. The data have been carefully checked for accuracy through dataentry editing and double-entry verification. There are occasional missing data. Minipills were in use by 5.54% (1,144) of the family planning patients studied. The analysis is limited to that portion of the data where sufficient numbers are available to allow breakdowns. Since the racial composition of the women screened is 88% black, white women are not included in this analysis. The number of women in the data base decreases sharply after 35 years of age. Thus only women 35 or under are analyzed. Also excluded from the analyses of blood pressure level are women currently on antihypertensive medications or for whom that information was unknown. A computer search was made matching all patient visits showing the same identifier. Several types of validity checks were made to assure that the data on two visits were from the same patient. The data were included only if there was a clear transition from nonhormonal methods to oral progestational agents for a minimum of 6 (and up to 24) months. New minipill users are thus excluded if they converted to oral progestational agents from hormonal methods such as combination-type oral contraceptives. Table I provides a derivation of the sample of women included in the analysis. A total of 17 1 women initiated minipill use from nonhormonal methods and completed 6 to 24 months’ follow-up: 119 new minipill users satisfy the study criteria. All of the study participants received 0.35 mg norethisterone. Results of the 119 minipill users are compared with those of 673 women with all of the above criteria except that they continued to use nonhormonal contraceptive methods during the follow-up interval. The nonhormonal methods included intrauterine device, foam and condoms, and diaphragm. The data are managed with the Dictionary-Driven Datasystem described by Blumenstein2 Statistical calculations are performed using the program SPSS.

Results Table II presents the mean age, body weight, percent ideal body weight, and baseline blood pressures of the 119 women initiating minipills, and the 673 women continuing nonhormonal contraceptive methods. The choice of contraceptive method was made by the pa-

Blood

pressure

Table I. Derivation minipill use

and oral progestational

agents

of sample of women

initiating

345

171

Women completing 2 6 months followup I

I 5

I 166

Unknown or positive history for antihypertensive medication

A

Missing or inconsistent data

White, or black >35 years of age

Negative history for antihypertensive medication

Id8

Complete data

Black and 535 years of age

tient and thus all characteristics of the groups are not necessarily comparable despite their similar initial age and blood pressure means. There are relatively fewer minipill users above the age of 25 years. Hence, the subsequent analyses of blood pressure changes are stratified into age categories. Fig. 1 presents the change in systolic blood pressure in the two groups, stratified by age. The mean increase in all nonhormonal users is 0.39 mm Hg; the mean increase in all minipill users is 1.73 mm Hg. The difference in systolic blood pressure rise between groups is not significant (p > 0.05). Fig. 2 presents the change in diastolic blood pressure in the two groups, stratified by age. The mean increase in all nonhormonal users is 1.23 mm Hg; the mean increase in all minipill users is 1.33 mm Hg. This group difference is not significant (p > 0.05). The mean group increase in systolic and diastolic blood pressure in minipill users is mainly attributable to the rise experienced by the 23 women in the age group 25 to 29 years. The mean blood pressure changes for this age group are not due to a few patients. The systolic pressure standard deviations for the ~19, 20 to 24, 25 to 29, and ~30 year age categories are 13.3, 15.2, 12.5, and 7.6 mm Hg, respectively. The diastolic pressure standard deviations for these same age groups are 13.6, 12.4, 11.2, and 11.8 mm Hg, respectively. Only five minipill users were in the 30 to 35 year age range, hence, it is difficult to make any inference about the effect of age on blood pressure change following minipill use. Sixteen of 663 (2.4%) nonhormonal users whose initial diastttlic blood pressure was <90 mm Hg developed a pressure 290 mm Hg on follow-up measure-

346

Hall et

ai.

February 1, 1980 Am. J. Obstet. Gynecol.

,

‘34

43

s-5,

48

,‘I

23

Fig. 1. Systolic blood pressure change classified by age in 119 minipill and 673 nonhormonal Table II. Initial characteristics contraceptive methods

of women

initiating

minipill

and of women

:wnipi11 (n = 119) I’MPan

‘Qe cy“) Aody weigh1 Ideal body weight (R) Systolic blood pressure (mm Hg) Diastolic blood pressure (mm Hg)

Standard

4.2 25.0 21.3

110.2 63.1

14.4 10.8

menr. None of the 119 minipill users developed a diastolic blood pressure ~90 mm Hg. Fig. 3 presents the weight change experienced by each of the two groups, stratified b? age. Change is standardized and expressed as the difference between the patient’s percent ideal body weight at the initial and final visit. ‘The mean increase in all nonhormonal users is 1.60; the mean increase in all minipill users is 3.27. The mean change in weight index between the two groups is marginally significant (p = 0.063) in the age stratified analysis of variance. Weight change is not significantly- related (p > 0.05) to blood pressure changes as determined by scattergram and correlation analvsis.

Comment A 5 year follow-up study of approximately 23.000 predominantly white women in the United Kingdom revealed a greater incidence of hypertension in women taking combination-type oral contraceptives which contained more than 3 mg of progestogen (usualI)- 4 mg of megestrol acetate or norethisterone acetate) when compared with brands which contained 3 mg or less of’ progestogen.” No evidence was found that estrogenic dosage (50 pg versus more than 50 pg) was related to

2Vonhormonal

dezktion

21.4 130.0 108.4

-

continuing

Mmn

21.9 140.3

116.2 112.Fi 64.4

users.

nonhormonal

(n = 673) Standard

deviation

4.6 33.4 25.4

Sign$cance

NS co.01

13.7


11.7

NS

the incidence of diagnosed hypertension. A subsequent report studied users of combination-type oral contraceptives containing the same estrogen dose (50 pg of ethinylestradiol) but varying doses of the progestogen. norethisterone acetate ( I, 3, and 4 mg). An increasing incidence of diagnosed hypertension was shown in users of higher doses of the progestogen.’ These data suggest that hypertension in long-term users of combination-type oral contraceptives might be related to the progestogen dose. In contrast, Weir and associatior? reported on blood pressure changes in 134 Scottish women after 2 years therapy with combination-type oral contraceptives rontaining similar estrogenic dosage (50 gg of mestranol or ethyinyl estradiol), but varying progestogen dosages (1 .O mg of norethisterone, 2.5 mg of lynestrenol. 3.0 mg of norethisterone, or 4.0 mg of megestrol) and found no evidence of greater blood pressure change with higher progestogen dosage. A limited number of clinical studies have evaluated blood pressure changes following the use of oral contraceptives which contain only progestogens (i.e., no estrogenic component). Some early reports indicated that rises of ~20 mm Hg systolic or diastolic blood pressure were seen in patients receiving norethis-

Volume Number

136 3

Blood


Fig. 2. Diastolic blood pressure

pressure

and oral progestational

agents,

347

20-24

change classified by age in 119 minipill and 673 nonhormonal

Fig. 3. Weight change classified by age in 119 minipill terone’j; others stated that hypertension had not been apparent in users of minipills containing 0.35 to 0.50 mg of megestrol acetate.’ The only previous longitudinal study of oral progestational agents in a predominantly black population is that reported in 1972 by Spellacy and Birk*: 103 postpartum women initiated contraceptive therapy with either norgestrel (0.075 mg, 71 women) or ethynodiol diacetate (0.25 mg, 32 women). The follow-up interval was limited to the first 6 months of therapy, but no significant increase in blood pressure was noted in either group; no patient developed hypertension defined as a systolic and diastolic blood pressure >140 and >90 mm Hg. The average weight gain was 2.7 pounds for the group receiving norgestrel and 1.2 pounds for the group receiving ethynodiol diacetate. . Our study includes prospective weight and blood pressure measurements before and after approximately 1 year of oral progestational therapy in 119 black women below the age of 35. The impressive weight gain observed in the minipill users was unexpected. The mean change in weight index is 3.3 following 6 to 24 months’ minipill therapy. Since the baseline

and 673 nonhormonal

users.

users.

average body weight was 130 pounds, this is equivalent to an average gain of 4.0 pounds during the study interval. The mean weight gain was greater than that documented in nonhormonal users. The interpretation of the greater increase in weight in the minipill group must take into account the difference in initial weight in the two groups (130.3 versus 140.3 pounds). However, the data suggest that substantial weight gain may be a side effect of minipill therapy. Our results indicate no statistically significant increase in either systolic or diastolic blood pressure in 119 initially normotensive black women followed for 6 to 24 months after initiation of contraceptive therapy with an oral progestogen. None of the patients developed a diastolic blood pressure of 90 mm Hg or more. These data: provide no evidence for an association betweep oral progestational contraceptive therapy (0.35 mg of norethisterone) and the development of elevated blood pressure in black women below age 35 remaining on minipill therapy for approximately 1 year. We intend to carefully follow the blood pressure levels of those women who continue minipill use for

348

Hall et

al.

February Am. .J. Obstet.

mcnc than 2 and up to 5 years. These data will provide additional information on whether or not long-term (2 to 5 vears) use of minipills is associated with any change

REFEREHCES

1. Kaplan, N. M.: Cardiovasculat complications of oral contraceptives, Ann. Rev. Med. 29~31, 1978. 2. Bfumenstein. B. A.: The Dictionary-Driven Datasystem, version 3.4, 1978, available from the Department of Biometry, Emory University, Atlanta, Georgia 30322. 3. Royal College of General Practitioners: Oral Contraceptives and Health, New York, 1974, Pitman Medical, p. 37. 4. Royal College of General Practitioners’ Oral Contraception Study: Effect on hypertension and benign breast disease of progestagen component in combined oral contraceptives, Lancet 1:6X, 1977. .‘j. Weir. R. J., Fraser, R., McElwee, G., Morton, J. .J,, Tree, M.. and Yonng.,J.: The effect of estrogen-progestc,gen oral

in either the blood pressure blood pressure elevation.

1. 1980 Gvnecol.

level or the incidcncc

contraceptives on blood pressure and on the reninangiotensin-aldosterone system, in Fregly, M. .J.. and Fregly, M. S. (editors): Oral Contraceptives and High Blood Pressure, Gainesville, Florida. 197-t. Dolphin Press, p. 68. 6. Bret, A. J., Blanchier, H., and Ramos, J. S.: t’rogcstatifs oraux et augmentation de la pression :IrtPriellk, Rev. Fr. Gynicol. Obstet. 63:703, 1968. 7. Nelson, J. H.: The use of the mini pill in private prar-tics, J. Reprod. Med. l&139, 1968. 8. Spellacy. IV. N., and Birk, S. A.: The effect of intrattterine devices, oral contraceptives, estrogens and progestogens on blood pressure, AM. J. ORSTET. GYNECXL 112:912, 1972.

Symposium on Approaches to the Birth Experience for the 1980’s A two-day Symposium on Approarhes to the Birth Experience for the 1980’s will be held at the Sheraton CIentre Hotel in New York, New York, March 1%13, 1980. ‘The svmposium program will he presented bv the Nurses Study Group of‘ the March of Dimes Birth Defects Foundation ( former-lv The National Foundation-March of Dimes). For further information. please contact:. March of Dimes Birth Defects Foundation. 62” Third Ave.. New York. Xc\+ York 100 17. 1

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