Contraception
461327-334,
1992
THE INFLUENCE OF A LOW-DOSE COMBINED ORAL CONTRACEPTIVE ON MENSTRUAL BLOOD LOSS AND IRON STATUS
Gerd Larsson’, Ian Milsom’, G&an Lindstedt2 and G&an Rybo’ l Department of Obstetrics and Gynecology, East Hospital, S-41 6 85 Ggteborg and the 2Department of Clinical Chemistry, Sahlgrens Hospital, University of GCiteborg, Sweden
ABSTRACT The influence of a low-dose combined oral contraceptive (ethinyl estradiol 30 pg + desogestrel 0.15 mg) on menstrual blood loss (MBL) was evaluated in 20 healthy, young women. MBL prior to commencing oral contraception was 60.2 + 5.6 ml (range 22-l 16 ml), and decreased (pcO.001) to 36.5 * 5.2 ml (range 7-80 ml) and 33.7 k 4.1 ml (range 5-70 ml) after 3 and 6 months’ oral contraceptive medication, respectively. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation. Five women had an MBL >80 ml prior to commencing oral contraceptive medication. In all of these women, MBL during the 6th menstrual period after commencing oral contraception was < 80 ml. All the women included in this study had a normal blood hemoglobin concentration, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 + 9.0 pg/l and was largely unchanged after 6 months’ oral contraception (39.7 + 6.3pg/l). On admission to the study, two women had a serum ferritin c 10 pg/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin concentration increased during oral contraceptive medication in both women (from 8.5 pg/l to 12.0 pg/l and from 5.4 p.g/l to 6.8 pg/l, respectively).The duration of menstruation (~~0.01) and the number of women suffering from dysmenorrhea (~~0.05) was reduced during oral contraception. Submitted for publication Accepted for publication
Copyright
June 8, 1992 August 17, 1992
Q 1992 Butterworth-Heinemann
328
Contraception
INTRODUCTION Approximately 180 million women worldwide use, or have used oral contraceptives for birth control. In the United States approximately 14 million women (32% of the women at risk for pregnancy) are current users of oral contraceptives.’ In 1987, Forrest2 reported that 77% of American women had used oral contraceptives at some point in their lives. Recent epidemiological studies from Sweden have reported that almost 90% of Swedish women have at some time in their lives taken the oral contraceptive pill.3V4 No single pharmacologic agent has been studied and reported on in greater detail than the oral contraceptive pill. Possible health benefits and health risks associated with oral contraceptives have been discussed and reviewed in detail both within the medical profession’ and by the news media. It is generally accepted that the use of combined oral contraceptives (OCs) reduces blood loss during the tablet-free week compared to the blood loss experienced during normal menstruation. However, surprisingly, there are few studies where the reduction in menstrual blood loss (MBL) during oral contraceptive medication has been assessed objectively.6-8 These studies, which were performed more than 20 years ago, were carried out in women using OCs containing considerably more estrogen and progestogen than is at present available in modern OCs. As far as we are aware, there are no reports on the objective assessment of menstrual blood loss during medication with low-dose combined monophasic or triphasic OCs. The aims of this study were: (a) to compare MBL during medication with a monophasic OC containing 30 ug ethinyl estradiol and 0.15 mg desogestrel with MBL during the period prior to commencing oral contraceptive medication; and (b) to determine if changes in MBL influenced iron stores.
MATERIAL
AND
METHODS
Twenty-three women who attended the Department of Obstetrics and requesting oral contraception Gynecology, East Hospital, Gbteborg, volunteered to participate in this study. All the women gave informed consent and the study was approved by the Ethical Committee, Faculty of Medicine, Gothenburg University. The women were healthy and none of them had a history or evidence of pelvic pathology as judged by clinical and gynecological examination. All the women had regular menstrual cycles, and at least six spontaneous menstrual periods after delivery, abortion or cessation of lactation, or a minimum of three spontaneous menstrual cycles after the use of hormonal or intrauterine contraception. Throughout the study the following medications were not permitted: antifibrinolytic drugs; prostaglandin synthetase inhibitors; acetylsalicylic acid; and iron supplementation. MBL was determined during one control cycle prior to commencing OC, during which time the women used barrier methods of contraception, and 3 and 6 months after commencing OC. The women were supplied with marked polythene bags for the collection of used sanitary pads and tampons. MBL
329
was measured for each day of menstruation and was calculated using the alkaline hematin method.gB’O Menstrual pattern, possible intermenstrual bleeding and dysmenorrhea were recorded during the control cycle prior to commencing OC and for the first 6 months of CC. Venous blood samples (one heparinized tube [lo ml] for blood hemoglobin and cell count, and one tube [lo ml] without anticoagulant for serum ferritin concentration analysis) were taken at the basal assessment prior to commencing OC, and after 3 and 6 months’ OC. Samples were obtained between 8.00 and 11.00 hrs, after a normal breakfast, on the 5th-12th day of the menstrual cycle. The women were instructed not to donate blood or perform blood tests during the study. Prolonged fasting was not permitted.” Hemoglobin, hematocrit and erythrocyte indices were analyzed the same day. Serum (5 ml) was immediately frozen for later analysis of serum ferritin by a double-antibody-polyethylene glycol radioimmunoassay (Diagnostic Products Corp., Los Angeles, CA, USA).” The properties of the assay in our hands have been described previously,’ ’ ,12 as have the results from a comparison with an immunoradiometric assay” and an immunochemi-luminometric assay.12 Results from in-house quality controls (pooled human serum) indicated absence of change in imprecision or bias in this study compared with previous studies and with results from a large international quality assessment programme. All samples were assayed within a few days. For each individual, all samples were positioned next to each other in the assay runs to ensure minimal influence of assay imprecision. Statistical analysis: The results are expressed as means + SEM. Duncan’s multiple range test was used for the evaluation of statistical significance (~~0.05 was considered to be statistically significant).
RESULTS None of the 23 women included in this study reported any serious side effects or complications, and no pregnancies occurred. Two women ceased taking OC during the 6-month observation period and were therefore excluded from the statistical analyses. One of the women ceased taking OC after 2 months because of nausea and one woman ceased after 3 months because of increased irritability. One woman was lost to follow-up due to the fact she emigrated 3 months after being included in the trial. Clinical details of the 20 women who completed the study were as follows: age 24.5 f 1.2 years, range 17-34 years; weight 64.0 f 1.7 kg, range 48-85 kg; height 170.5 f 1.l cm, range 162-177 cm; parity 0.8 f 0.3, range O-l. All the women had a regular menstrual cycle before commencing oral contraceptive medication. Intermenstrual bleeding was reported by 5 women during the first 3 menstrual cycles after commencing oral contraception. Only one woman reported intermenstrual bleeding during the 6th menstrual cycle after commencing oral contraception. The duration of menstruation decreased (~~0.01) from 5.2 f 0.2 days prior to commencing oral contraception to 4.5 + 0.1 days during oral contraception. There was no significant change in the interval between menstruations after commencing oral contraception. The
Contraception
330
number of women who reported dysmenorrhea decreased (~~0.05) from 14 prior to commencing oral contraception to 4 after commencing oral contraception. MBL prior to commencing OC was 60.2 + 5.6 ml (range 22-l 16 ml), and decreased (p80 ml at the basal assessment prior to commencing OC medication. All of these women had an MBL < 80 ml after 6 months OC (Fig 1). Daily menstrual blood loss before, and after 3 and 6 months’ oral contraceptive medication is shown in Fig. 2. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation.
MBL, ml
Before
OC
3 months
6 months
Fig.1. Individual values of menstrual blood loss (MBL) before, and 3 and 6 months after commencing oral contraceptive medication (n = 20). All the women included in this study had a normal blood hemoglobin count, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 +_9.0 ).tg/l and was largely unchanged after 3 (42.5 + 7.2pg/l) and 6 months’ oral contraception (39.7 + 6.3pg/l). Serum ferritin concentration for the five women with a menstrual blood loss > 80 ml at the baseline assessment was 25.0 f 7.8 p@l compared to 54.9 +- 12.1 Kg/l for the fifteen women with a menstrual blood loss < 80 ml at the basal assessment. On admission to the study, two women had a serum ferritin concentration c 10 ug/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin
Contraception
331
increased during oral contraceptive medication in both women (from 8.5 ug/l to 12.0 pg/l and from 5.4 ug/l to 6.8 us/l, respectively).
30
1
I
IT
MBL, ml
n Baseline Kl 3 months
q
1
2
3
6 months
4
5
6
7
DAY OF MENSTRUATION Fig. 2. Daily menstrual blood loss (MBL) expressed as mean + SEM before, and 3 and 6 months after commencing oral contraceptive medication (n = 20). Significance of difference (Duncan’s multiple range test) with baseline values is indicated when applicable by: * = ~~0.05; ** = ~~0.01
DISCUSSION It is generally accepted that menstrual blood loss decreases in women using oral contraception. This observation has been confirmed objectively.6-8 Several different oral contraceptive combinations have been shown to reduce menstrual blood loss by approximately 40-50%.6*7 However, these studies which were performed more than 20 years ago, were carried out in women using combined oral contraceptives containing quantities of estrogen and progestagen well in excess of those found in modern oral contraceptives now in use. The results of the present study have clearly shown that a modern lowdose combined oral contraceptive, containing 30 pg ethinyl estradiol and 0.15 mg desogestrel, reduced menstrual blood loss by approximately 44%.
332
Contraception
The mode of action of this reduction in menstrual blood loss by combined oral contraceptives is known to be due to several different mechanisms. Atrophy of the endometrium is considered to be the main reason for the reduction in menstrual blood loss induced by oral contraceptives.s The spiral arteries in the endometrium of women exposed to combined oral contraceptives have been shown to be poorly developed or absent in large areas of the endometrium.13 In this respect, the potency of the gestagen component of the oral contraceptive to induce endometrial inhibition seems to be of particular importance.14 Oral contraceptives are also known to influence coagulation and fibrinolysis’5 as well as prostaglandin synthesis,16 which may also contribute to the observed changes in menstrual blood loss during oral contraceptive medication. In a randomly selected Swedish population, the average menstrual blood loss has been reported to be 43 ml per period.” In the present study, the mean menstrual blood loss was 60.2 ml prior to commencing oral contraceptive medication which is somewhat in excess of that reported earlier.” A possible explanation for the higher MBL in the present study is the fact that 5 of the 20 women had an MBL >80 ml at the basal assessment prior to commencing OC medication. Earlier population studies have shown that approximately 10% of healthy women suffer from menorrhagia, defined as a menstrual blood loss > 80 ml.‘7~16 The etiology of idiopathic menorrhagia is extremely complex.‘g Among the many factors implicated in the control of menstrual blood loss are prostaglandins, coagulation, fibrinolysis and platelet activity. Women suffering from menorrhagia have been shown to have elevated endometrial concentrations of the prostaglandins PGF2o and PGEz2’ and an increased fibrinolytic activity.2’ Antifibrinolytic agents, prostaglandin synthetase inhibitors, the intrauterine release of progesterone and oral contraceptives have been shown to be effective in the medical treatment of menorrhagia.6s22-27 Oral contraceptives have been shown to influence several of the mechanisms involved in the control of menstrual blood loss.8~13~‘5~‘6 The reported efficacy of oral contraceptives in the treatment of menorrhagia has been largely based on the studies performed in the late 60’s using potent combined oral contraceptives that were available at that time.’ In the present study, five women were found to have a menstrual blood loss of > 80 ml prior to commencing oral contraception. All five women were later found to have a menstrual blood loss c 80 ml during medication with the low-dose combined oral contraceptive under investigation.
ACKNOWLEDGEMENTS This study was supported by grants from Hjalmar Svensson’s Fund, Gothenburg Medical Society and the University of Gdteborg. We also wish to thank Mijlnlycke AB for the kind donation of pads used in this study.
Contraception
333
REFERENCES 1.
Adams Hillard PJ. The patients’ reaction to side effects of oral contraceptives. Am J Obstet Gynecol 1989;161 :1412-l 5.
2.
Forrest JD. Has she or hasn’t she? U.S. women’s experience with contraception. Fam Plann Perspect 1987;19:133.
3.
Riphagen FE, von Schoultz B. Contraception in Sweden. Contraception 1989;39:633-42.
4.
Milsom I, Sundell G, Andersch B. A longitudinal study of contraception and pregnancy outcome in a representative sample of young Swedish women. Contraception 1991;43:111-19
5.
Mishell DR Jr. Medical progress: Contraception. N Engl J Med 1989;320:777-87.
6.
Nilsson L, Solvell L. Clinical studies on oral contraceptives - a randomized double-blind cross-over study of 4 different preparations Anovlar mite, Lyndiol mite Ovulen and Volidan. Acta Obstet Gynecol Stand 1967;Suppl 8:3-31.
7.
Nilsson L , Solve11 L. A clinical study on a sequential oral contraceptive Ovisec. Acta Obstet Gynecol Stand 1968;Suppl 6:3-25.
8.
Nilsson L, Rybo G. Treatment of menorrhagia. Am J Obstet Gynecol 1971 ;l lo:71 3-20.
9.
Hallberg L, Nilsson L. Determination of menstrual blood loss. Stand J Clin Lab Invest 1964;16:244-48.
10.
Newton J, Barnard G, Collins W. A rapid method for measuring menstrual blood loss using automatic extraction. Contraception 1977;16:269-82.
11.
Lundberg P-A, Lindstedt G, Andersson T, Branegard B, Lundquister G, Nystrom E. Increase in serum ferritin concentration induced by fasting. Clin Chem 1984;30:161-63.
12.
Milsom I, Rybo G, Lindstedt G. The influence of copper surface area on menstrual blood loss and iron status in women fitted with an IUD. Contraception 1990;41:271-81.
13.
Friedich ER. Effects of contraceptive preparations on the fine structure of the endometrium. Obstet Gynecol 1967;30:201-13.
14.
Hourihan HM, Sheppard BL, Bonnar J. The morphological response of blood vessels of the endometnum to low-dose oral norethisterone and levonorgestrel. J Obstet Gynaecol 1991 ;l1:47-54.
-
334
Contraception
15.
Siegbahn A, Ruusuvaara L. Age dependence of blood fribrinolytic components and the effects of low-dose contraceptives on coagulation and fibrinolysis in teenagers. Thromb Haemostas 1988;60:361-64.
16.
Lundstrom V, Green K. Endogenous levels of prostaglandin Fpo and its metabolites in plasma and endometrium of normal and dysmenorrheic women. Am J Obstet Gynecol 1978;130:640-46.
17.
Hallberg L, Hogdahl AM, Nilsson L, Rybo G. Menstrual blood loss a population study. Acta Obstet Gynecol Stand 1966;45:320-51.
18.
Van Eijkeren MA, Christiaens GCML, Sixma JJ, Haspels AA. Menorrhagia: A review. Obstet Gynecol Surv 1989;44:421-29.
19.
Rees MCP. Heavy, painful periods. Clin Obstet Gynaecol 1989;3:34156.
20.
Willman EA, Collins WP, Clayton SG. Studies in the involvement of prostaglandins in uterine symptomatology and pathology Brit J Obstet Gynaecol 1976;83:337-41.
21.
Rybo G. Clinical and experimental studies on menstrual blood loss. Acta Obstet Gynecol Stand 1966;45:1-45.
22.
Anderson ABM, Haynes PJ, Guillebaud J, Turnbull AC. Reduction of menstrual blood loss by prostaglandin synthetase inhibitors. Lancet 1976:i:774-76.
23.
Bergqvist A, Rybo G. Treatment of menorrhagia with intrauterine release of progesterone. Br J Obstet Gynaecol 1983;90:255-58.
24.
Andersch B, Milsom I. An objective evaluation of flurbiprofen and tranexamic acid in the treatment of idiopathic menorrhagia. Acta Obstet Gynaecol Stand 1988;67:645-48.
25.
Andersson K, Rybo G. Levonorgestrel-releasing intrauterine device in treatment of menorrhagia. Brit J Obstet Gynaecol 1990;97:690-94.
26.
Macdonald R. Modern treatment of menorrhagia. Brit J Obstet Gynaecol 1990;97:3-7.
27.
Milsom I, Andersson K, Andersch B, Rybo G. A comparison of flurbiprofen, tranexamic acid and a levonorgestrel-releasing intrauterine device in the treatment of idiopathic menorrhagia. Am J Obstet Gynecol 1991 ;164:879-83.
461327-334,
1992
THE INFLUENCE OF A LOW-DOSE COMBINED ORAL CONTRACEPTIVE ON MENSTRUAL BLOOD LOSS AND IRON STATUS
Gerd Larsson’, Ian Milsom’, G&an Lindstedt2 and G&an Rybo’ l Department of Obstetrics and Gynecology, East Hospital, S-41 6 85 Ggteborg and the 2Department of Clinical Chemistry, Sahlgrens Hospital, University of GCiteborg, Sweden
ABSTRACT The influence of a low-dose combined oral contraceptive (ethinyl estradiol 30 pg + desogestrel 0.15 mg) on menstrual blood loss (MBL) was evaluated in 20 healthy, young women. MBL prior to commencing oral contraception was 60.2 + 5.6 ml (range 22-l 16 ml), and decreased (pcO.001) to 36.5 * 5.2 ml (range 7-80 ml) and 33.7 k 4.1 ml (range 5-70 ml) after 3 and 6 months’ oral contraceptive medication, respectively. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation. Five women had an MBL >80 ml prior to commencing oral contraceptive medication. In all of these women, MBL during the 6th menstrual period after commencing oral contraception was < 80 ml. All the women included in this study had a normal blood hemoglobin concentration, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 + 9.0 pg/l and was largely unchanged after 6 months’ oral contraception (39.7 + 6.3pg/l). On admission to the study, two women had a serum ferritin c 10 pg/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin concentration increased during oral contraceptive medication in both women (from 8.5 pg/l to 12.0 pg/l and from 5.4 p.g/l to 6.8 pg/l, respectively).The duration of menstruation (~~0.01) and the number of women suffering from dysmenorrhea (~~0.05) was reduced during oral contraception. Submitted for publication Accepted for publication
Copyright
June 8, 1992 August 17, 1992
Q 1992 Butterworth-Heinemann
328
Contraception
INTRODUCTION Approximately 180 million women worldwide use, or have used oral contraceptives for birth control. In the United States approximately 14 million women (32% of the women at risk for pregnancy) are current users of oral contraceptives.’ In 1987, Forrest2 reported that 77% of American women had used oral contraceptives at some point in their lives. Recent epidemiological studies from Sweden have reported that almost 90% of Swedish women have at some time in their lives taken the oral contraceptive pill.3V4 No single pharmacologic agent has been studied and reported on in greater detail than the oral contraceptive pill. Possible health benefits and health risks associated with oral contraceptives have been discussed and reviewed in detail both within the medical profession’ and by the news media. It is generally accepted that the use of combined oral contraceptives (OCs) reduces blood loss during the tablet-free week compared to the blood loss experienced during normal menstruation. However, surprisingly, there are few studies where the reduction in menstrual blood loss (MBL) during oral contraceptive medication has been assessed objectively.6-8 These studies, which were performed more than 20 years ago, were carried out in women using OCs containing considerably more estrogen and progestogen than is at present available in modern OCs. As far as we are aware, there are no reports on the objective assessment of menstrual blood loss during medication with low-dose combined monophasic or triphasic OCs. The aims of this study were: (a) to compare MBL during medication with a monophasic OC containing 30 ug ethinyl estradiol and 0.15 mg desogestrel with MBL during the period prior to commencing oral contraceptive medication; and (b) to determine if changes in MBL influenced iron stores.
MATERIAL
AND
METHODS
Twenty-three women who attended the Department of Obstetrics and requesting oral contraception Gynecology, East Hospital, Gbteborg, volunteered to participate in this study. All the women gave informed consent and the study was approved by the Ethical Committee, Faculty of Medicine, Gothenburg University. The women were healthy and none of them had a history or evidence of pelvic pathology as judged by clinical and gynecological examination. All the women had regular menstrual cycles, and at least six spontaneous menstrual periods after delivery, abortion or cessation of lactation, or a minimum of three spontaneous menstrual cycles after the use of hormonal or intrauterine contraception. Throughout the study the following medications were not permitted: antifibrinolytic drugs; prostaglandin synthetase inhibitors; acetylsalicylic acid; and iron supplementation. MBL was determined during one control cycle prior to commencing OC, during which time the women used barrier methods of contraception, and 3 and 6 months after commencing OC. The women were supplied with marked polythene bags for the collection of used sanitary pads and tampons. MBL
329
was measured for each day of menstruation and was calculated using the alkaline hematin method.gB’O Menstrual pattern, possible intermenstrual bleeding and dysmenorrhea were recorded during the control cycle prior to commencing OC and for the first 6 months of CC. Venous blood samples (one heparinized tube [lo ml] for blood hemoglobin and cell count, and one tube [lo ml] without anticoagulant for serum ferritin concentration analysis) were taken at the basal assessment prior to commencing OC, and after 3 and 6 months’ OC. Samples were obtained between 8.00 and 11.00 hrs, after a normal breakfast, on the 5th-12th day of the menstrual cycle. The women were instructed not to donate blood or perform blood tests during the study. Prolonged fasting was not permitted.” Hemoglobin, hematocrit and erythrocyte indices were analyzed the same day. Serum (5 ml) was immediately frozen for later analysis of serum ferritin by a double-antibody-polyethylene glycol radioimmunoassay (Diagnostic Products Corp., Los Angeles, CA, USA).” The properties of the assay in our hands have been described previously,’ ’ ,12 as have the results from a comparison with an immunoradiometric assay” and an immunochemi-luminometric assay.12 Results from in-house quality controls (pooled human serum) indicated absence of change in imprecision or bias in this study compared with previous studies and with results from a large international quality assessment programme. All samples were assayed within a few days. For each individual, all samples were positioned next to each other in the assay runs to ensure minimal influence of assay imprecision. Statistical analysis: The results are expressed as means + SEM. Duncan’s multiple range test was used for the evaluation of statistical significance (~~0.05 was considered to be statistically significant).
RESULTS None of the 23 women included in this study reported any serious side effects or complications, and no pregnancies occurred. Two women ceased taking OC during the 6-month observation period and were therefore excluded from the statistical analyses. One of the women ceased taking OC after 2 months because of nausea and one woman ceased after 3 months because of increased irritability. One woman was lost to follow-up due to the fact she emigrated 3 months after being included in the trial. Clinical details of the 20 women who completed the study were as follows: age 24.5 f 1.2 years, range 17-34 years; weight 64.0 f 1.7 kg, range 48-85 kg; height 170.5 f 1.l cm, range 162-177 cm; parity 0.8 f 0.3, range O-l. All the women had a regular menstrual cycle before commencing oral contraceptive medication. Intermenstrual bleeding was reported by 5 women during the first 3 menstrual cycles after commencing oral contraception. Only one woman reported intermenstrual bleeding during the 6th menstrual cycle after commencing oral contraception. The duration of menstruation decreased (~~0.01) from 5.2 f 0.2 days prior to commencing oral contraception to 4.5 + 0.1 days during oral contraception. There was no significant change in the interval between menstruations after commencing oral contraception. The
Contraception
330
number of women who reported dysmenorrhea decreased (~~0.05) from 14 prior to commencing oral contraception to 4 after commencing oral contraception. MBL prior to commencing OC was 60.2 + 5.6 ml (range 22-l 16 ml), and decreased (p80 ml at the basal assessment prior to commencing OC medication. All of these women had an MBL < 80 ml after 6 months OC (Fig 1). Daily menstrual blood loss before, and after 3 and 6 months’ oral contraceptive medication is shown in Fig. 2. The reduction in MBL during oral contraception was most apparent during the first two days of menstruation.
MBL, ml
Before
OC
3 months
6 months
Fig.1. Individual values of menstrual blood loss (MBL) before, and 3 and 6 months after commencing oral contraceptive medication (n = 20). All the women included in this study had a normal blood hemoglobin count, hematocrit and erythrocyte indices and there were no significant changes in these variables during the course of the study. Serum ferritin concentration prior to commencing oral contraception was 44.2 +_9.0 ).tg/l and was largely unchanged after 3 (42.5 + 7.2pg/l) and 6 months’ oral contraception (39.7 + 6.3pg/l). Serum ferritin concentration for the five women with a menstrual blood loss > 80 ml at the baseline assessment was 25.0 f 7.8 p@l compared to 54.9 +- 12.1 Kg/l for the fifteen women with a menstrual blood loss < 80 ml at the basal assessment. On admission to the study, two women had a serum ferritin concentration c 10 ug/l, indicative of low iron stores. Both these women had an MBL > 80 ml at the baseline assessment. Serum ferritin
Contraception
331
increased during oral contraceptive medication in both women (from 8.5 ug/l to 12.0 pg/l and from 5.4 ug/l to 6.8 us/l, respectively).
30
1
I
IT
MBL, ml
n Baseline Kl 3 months
q
1
2
3
6 months
4
5
6
7
DAY OF MENSTRUATION Fig. 2. Daily menstrual blood loss (MBL) expressed as mean + SEM before, and 3 and 6 months after commencing oral contraceptive medication (n = 20). Significance of difference (Duncan’s multiple range test) with baseline values is indicated when applicable by: * = ~~0.05; ** = ~~0.01
DISCUSSION It is generally accepted that menstrual blood loss decreases in women using oral contraception. This observation has been confirmed objectively.6-8 Several different oral contraceptive combinations have been shown to reduce menstrual blood loss by approximately 40-50%.6*7 However, these studies which were performed more than 20 years ago, were carried out in women using combined oral contraceptives containing quantities of estrogen and progestagen well in excess of those found in modern oral contraceptives now in use. The results of the present study have clearly shown that a modern lowdose combined oral contraceptive, containing 30 pg ethinyl estradiol and 0.15 mg desogestrel, reduced menstrual blood loss by approximately 44%.
332
Contraception
The mode of action of this reduction in menstrual blood loss by combined oral contraceptives is known to be due to several different mechanisms. Atrophy of the endometrium is considered to be the main reason for the reduction in menstrual blood loss induced by oral contraceptives.s The spiral arteries in the endometrium of women exposed to combined oral contraceptives have been shown to be poorly developed or absent in large areas of the endometrium.13 In this respect, the potency of the gestagen component of the oral contraceptive to induce endometrial inhibition seems to be of particular importance.14 Oral contraceptives are also known to influence coagulation and fibrinolysis’5 as well as prostaglandin synthesis,16 which may also contribute to the observed changes in menstrual blood loss during oral contraceptive medication. In a randomly selected Swedish population, the average menstrual blood loss has been reported to be 43 ml per period.” In the present study, the mean menstrual blood loss was 60.2 ml prior to commencing oral contraceptive medication which is somewhat in excess of that reported earlier.” A possible explanation for the higher MBL in the present study is the fact that 5 of the 20 women had an MBL >80 ml at the basal assessment prior to commencing OC medication. Earlier population studies have shown that approximately 10% of healthy women suffer from menorrhagia, defined as a menstrual blood loss > 80 ml.‘7~16 The etiology of idiopathic menorrhagia is extremely complex.‘g Among the many factors implicated in the control of menstrual blood loss are prostaglandins, coagulation, fibrinolysis and platelet activity. Women suffering from menorrhagia have been shown to have elevated endometrial concentrations of the prostaglandins PGF2o and PGEz2’ and an increased fibrinolytic activity.2’ Antifibrinolytic agents, prostaglandin synthetase inhibitors, the intrauterine release of progesterone and oral contraceptives have been shown to be effective in the medical treatment of menorrhagia.6s22-27 Oral contraceptives have been shown to influence several of the mechanisms involved in the control of menstrual blood loss.8~13~‘5~‘6 The reported efficacy of oral contraceptives in the treatment of menorrhagia has been largely based on the studies performed in the late 60’s using potent combined oral contraceptives that were available at that time.’ In the present study, five women were found to have a menstrual blood loss of > 80 ml prior to commencing oral contraception. All five women were later found to have a menstrual blood loss c 80 ml during medication with the low-dose combined oral contraceptive under investigation.
ACKNOWLEDGEMENTS This study was supported by grants from Hjalmar Svensson’s Fund, Gothenburg Medical Society and the University of Gdteborg. We also wish to thank Mijlnlycke AB for the kind donation of pads used in this study.
Contraception
333
REFERENCES 1.
Adams Hillard PJ. The patients’ reaction to side effects of oral contraceptives. Am J Obstet Gynecol 1989;161 :1412-l 5.
2.
Forrest JD. Has she or hasn’t she? U.S. women’s experience with contraception. Fam Plann Perspect 1987;19:133.
3.
Riphagen FE, von Schoultz B. Contraception in Sweden. Contraception 1989;39:633-42.
4.
Milsom I, Sundell G, Andersch B. A longitudinal study of contraception and pregnancy outcome in a representative sample of young Swedish women. Contraception 1991;43:111-19
5.
Mishell DR Jr. Medical progress: Contraception. N Engl J Med 1989;320:777-87.
6.
Nilsson L, Solvell L. Clinical studies on oral contraceptives - a randomized double-blind cross-over study of 4 different preparations Anovlar mite, Lyndiol mite Ovulen and Volidan. Acta Obstet Gynecol Stand 1967;Suppl 8:3-31.
7.
Nilsson L , Solve11 L. A clinical study on a sequential oral contraceptive Ovisec. Acta Obstet Gynecol Stand 1968;Suppl 6:3-25.
8.
Nilsson L, Rybo G. Treatment of menorrhagia. Am J Obstet Gynecol 1971 ;l lo:71 3-20.
9.
Hallberg L, Nilsson L. Determination of menstrual blood loss. Stand J Clin Lab Invest 1964;16:244-48.
10.
Newton J, Barnard G, Collins W. A rapid method for measuring menstrual blood loss using automatic extraction. Contraception 1977;16:269-82.
11.
Lundberg P-A, Lindstedt G, Andersson T, Branegard B, Lundquister G, Nystrom E. Increase in serum ferritin concentration induced by fasting. Clin Chem 1984;30:161-63.
12.
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