The Relationship between Long-Distance Running, Plasma Progesterone, and Luteal Phase Length

FERTILITY AND STERILITY Copyright 0 1979 The American Fertility Society

Vol. 31, No. 2, February 1979 Printed in U.SA.

THE RELATIONSHIP BETWEEN LONG-DISTANCE RUNNING, PLASMA PROGESTERONE, AND LUTEAL PHASE LENGTH

MONA SHANGOLD, M.D.* RUTH FREEMAN, M.D. BENJAMIN THYSEN, PH.D. MICHAEL GATZ, B.S. Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, Bronx, New York 10461

The chronic effects of long-distance running upon the menstrual cycle were studied in a healthy, ovulatory 30-year-old woman. Luteal phase plasma concentrations of follicle-stimulating hormone, luteinizing hormone, 17fJ-estradiol, and progesterone were compared during a control and a training cycle. The luteal phase was shorter in cycles of greater mileage. Mid-luteal phase plasma progesterone concentrations were significantly lower during training. Fertil SteriI31:130, 1979

Few studies have been done relating athletic training to reproductive hormones. A number of investigators have reported the acute effects of exercise upon peripheral concentrations ofluteinizing hormone (LID and androgens in men. l -3 Fewer reports have described acute changes in hormone concentrations in exercising women. I. 4 Little is known about the chronic effects of exercise upon gonadotropin and ovarian steroid concentrations in women athletes. It was the purpose of this study to investigate the effect of distance running upon the menstrual cycle and to compare hormone concentrations throughout the luteal phase during control and training cycles. MATERIALS AND METHODS

A healthy 30-year-old woman of normal weight and body fat composition and taking no hormonal medication was the subject of this three-part study. In the first part, heparinized venous blood Received August I, 1978; accepted August 21, 1978. *Reprint requests: Mona Shangold, M.D., Department of Obstetrics and Gynecology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, N.Y. 10461.

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samples were obtained daily for determinations of follicle-stimulating hormone ·(FSH), LH, 17{3-estradiol (E 2 ), and progesterone throughout the luteal ph~ses of a control cycle and a training cycle: Two samples from each were also assayed for prolactin. In the control cycle, the subject ran an average of 26 miles/week during the follicular phase and none during the luteal phase; in the training cycle, she ran an average of 20 miles! week during both follicular and luteal phases. Work-out distances ranged from 3 to 6 miles. All running was at a pace between 6 and 7 mileslhour. Changes in weekly mileages were gradual. Ambient temperature changes were negligible. No, samples were drawn less than 16 hours after the previous run. Mean weight varied ± 1 pound. In the second part of the study, weekly mileage was compared with luteal phase length during 18 cycles in the same subject. Cycles were of normal length before, during, and after a long-distance training program (range: 25 to 32 days). Mean weight varied±5 pounds. The length of the luteal phase was based on cervical mucus changes in all cycles, after determining in a few cycles that the mucus consistently changed 2 days following the LH surge; basal body temperatures were biphasic.

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LONG-DISTANCE RUNNING, PLASMA PROGESTERONE, AND LUTEAL PHASE LENGTH

In the third part of the study, seven mid-luteal phase blood samples from three control cycles and seven from three training cycles were collected from 3 to 7 days after the mucus change in each and assayed for plasma LH and progesterone levels. Average weekly mileages during the luteal phases were 2, 2, and 0 during th( three control cycles and 32, 21, and 16 during the three training cycles. FSH and LH were quantitated by double-antibody radioimmunoassay procedures utilizing 1251_ labeled tracer, based on the methods of Midgley5 for FSH and Odell et al. 6 for LH. Concentrations of E2 were determined by radioimmunoassay according to the method of Wright et aU Progesterone levels were assayed by radioimmunoassay based on the method of Abraham et al. 8 Prolactin concentrations were determined by radioimmunoassay according to the method of Sinha et al. 9 All assays were done in duplicate. The inter- and intra-assay coefficients of variation in this laboratory are <15% and <10%, respectively. Statistical analysis of the data was carried out by paired or unpaired two-tailed t-test and leastsquare linear regression.

RESULTS

Mid-luteal phase plasma progesterone concentrations were higher during the control cycle than during the training cycle, with peaks of 30.2 and 9.0 ng/ml, respectively (P < 0.01) (Fig. 1). Slightly, but not significantly, higher E2 and LH levels were noted during the luteal phase of the control cycle, with midluteal peaks of 255.6 (control) and 167.3 pg/ml (training) for E2 and peaks of 17.2 and less than 2.5 mIU/ml, respectively, for LH. FSH levels appeared similar in the two cycles. Menstruation began 13 days after the LH surge in the control cycle and 11 days after the LH surge in the training cycle. In the 18 cycles studied, the length of the luteal phase varied inversely with the average weekly mileage run during the luteal phase (y = 13.0 0.10x; r = - 0.70; P < 0.005). An inverse relationship was also shown between the length of the luteal phase and the total distance run during the first 7 days of the follicular phase (y = 13.3 - O.llx; r = - 0.81; P < 0.001) (Fig. 2). The luteal phase was 13 to 14 days in cycles in which fewer than 5 miles/week w~re run and was 9 days or less in cycles in which running was greater than 35 miles/week. No relationship was found between

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FIG. 1. Daily plasma concentrations of LH, FSH, E 2 , and progesterone during luteal phases of control and training cycles. Next menses are indicated by arrows.

total cycle length (menstrual interval) and weekly mileage. Seven mid-luteal phase progesterone concentrations from three control cycles were significantly higher than those from three training cycles: control, 23.7 ± 2.90 ng/ml (mean ± standard error); training, 8.2 ± 0.85 ng/ml; P < 0.001 (Fig. 3). The LH concentrations in the three control cycles did not differ significantly from the LH concentrations in the three training cycles. No significant relationship was found between the midluteal phase LH values and the corresponding progesterone values. Plasma prolactin concentrations during the luteal phase of the control cycle were 15.9 and 10.3 ng/ml; comparable samples from the training cycle were 13.2 and 10.9 ng/ml. In another study, the plasma prolactin concentrations of this subject, determined within 1 hour after runs of 21 miles and 8 miles, were 18.5 and 22.2 ng/ml, respectively. (Normal, in this laboratory, is less than 28 ng/ml.)

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SHANGOLD ET AL.

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We have demonstrated decreased progesterone levels in the luteal phase of a subject during chronic long distance running. The alteration in progesterone concentration and luteal phase length during increased luteal phase running, following controlled follicular phase running, suggests that running during the luteal phase has a direct effect on that portion of the cycle. The reduction in progesterone may be due to decreased production, increased metabolism or increased clearance. Jones lO has described luteal insuffi30

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February 1979

ciency due to ovarian defects, defects of the hypothalamic-pituitary axis, metabolic defects, and specific defects in luteal cell steroidogenesis. Sherman and Korenman l l found decreased concentrations of progesterone and E2 in women with short luteal phases, compared with normal women. Sherman and Korenman l2 reported that women with luteal phases of normal length but reduced progesterone concentrations had low FSH concentrations during the follicular phase; they suggested that the short luteal phase and the inadequate luteal phase might be related to deficient FSH secretion during the follicular phase. The association in our subject of a short luteal phase with increased running during the early follicular phase might support the concept that dysfunction of follicular maturation may lead to luteal phase insufficiency. However, in the two cycles of daily sampling, the only significant difference in mileage run occurred during the luteal phase. While the difference in the heights of the LH surges (control cycle to 81.0 mIU/ml and training cycle to 53.0 mIU/ml) probably reflects the inadequacy of once-daily sampling for a substance with rapidly changing concentrations, a slight difference in mid-luteal phase LH levels may be responsible for differences in progesterone concentrations. Rowell et aU 3 have shown decreased hepatic blood flow during exercise. Radigan and Robinson l4 have shown decreased renal blood flow during exercise. Such changes may explain alterations in metabolic clearance rates and provide an explanation for the increases in progesterone levels during the acute exercise period reported by Jurkowski et al. 4 This mechanism offers no clue to the decreased concentrations found nonacutely during long-term exercise in our subject. Little information is presently available on alterations of progesterone metabolism with exercise. Seppala et al. 15 and Del Pozo et al. 16 have described hyperprolactinemia as a cause of luteal insufficiency. The normal prolactin concentrations in our subject make this an unlikely cause, even though prolactin is normally secreted in response to exerciseY Although the control progesterone values in this subject were higher than reported by many authors, Abraham et al. 18 have reported even higher progesterone concentrations in normal subjects, determined by the same method. Our data provide evidence for a potential cause of infertility in women long-distance runners. Since the men-

Vol. 31, No.2

LONG-DISTANCE RUNNING, PLASMA PROGESTERONE, AND LUTEAL PHASE LENGTH

strual interval remained normal, the observed changes in hormone concentrations and luteal phase length would not have been detected if the present study had not been undertaken for investigative purposes. The incidence of similar changes among athletes remains unknown. Since the lowest effective hormone concentrations and the shortest effective durations of action for hormones (at endometrial and other target sites) are not known,· the significance of such luteal phase alterations requires further investigation.

REFERENCES 1. Sutton J, Coleman M, Casey J, Lazarus L: Androgen responses during physical exercise. Br Med J 1:520, 1973 2. Dessypris A, Kuoppasalmi K, Adlercreutz H: Plasma cortisol, testosterone, androstenedione and luteinizing hormone (LH) in a non-competitive marathon run. J Steroid Biochem 7:33, 1976 3. Kuoppasalmi K, Naveri H, Rehunen S, Harkonen M, Adlercreutz H: Effect of strenuous anaerobic running exercise on plasma growth hormone, cortisol, luteinizing hormone, testosterone, androstenedione, estrone and estradiol. J Steroid Biochem 7:823, 1976 4. Jurkowski J, Jones N, Walker W, Younglai E, Sutton J: Ovarian hormonal responses to exercise. J Appl Physiol 44:109,1978 5. Midgley A: Radioimmunoassay for human follicle-stimulating hormone. J Clin Endocrinol Metab 27:295, 1967 6. Odell W, Ross G, Rayford P: Radioimmunoassay for human luteinizing hormone. Metabolism 15:287, 1966

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7. Wright K, Collins D, Preedy J: Comparative specificity of antisera raised against estrone, estradiol-17{3 and estriol using W-carboxy-methyloxime bovine serum albumin derivatives. Steroids 21:755, 1973 8. Abraham G, Swerdloff R, Tulchinsky D, Odell W: Radioimmunoassay of plasma progesterone. J Clin Endocrinol Metab 32:619, 1971 9. Sinha Y, Selby F, Lewis U, Vanderlaan W: A homologous radioimmunoassay for human prolactin. J Clin Endocrinol Metab 36:509, 1973 10. Jones G: The luteal phase defect. Fertil SteriI27:351, 1976 11. Sherman B, Korenman S: Measurement of plasma LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the short luteal phase. J Clin Endocrinol Metab 38:89, 1974 12. Sherman B, Korenman S: Measurement of serum LH, FSH, estradiol and progesterone in disorders of the human menstrual cycle: the inadequate luteal phase. J Clin Endocrinol Metab 39:145, 1974 13. Rowell L, Blackmon J, Bruce R: Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J Clin Invest 43:1677,1964 14. Radigan L, Robinson S: Effects of environmental heat stress and exercise on renal blood flow and filtration rate. J Appl PhysioI2:185, 1949 15. Seppala M, Hirvonen E, Ranta T: Hyperprolactinaemia and luteal insufficiency. Lancet 1:229, 1976 16. Del Pozo E, Wyss H, Lancranjan I, Obolensky W, Varga L: Prolactin-induced luteal insufficiency and its treatment with bromocriptin: preliminary results. In Ovulation in the Human, Edited by PG Crosignani, DR Mishell. London, Academic Press, 1976, p 297 17. Williams R: Textbook of Endocrinology . Philadelphia, WB Saunders Co, 1974, p 49 18. Abraham G, Maroulis G, Marshall J: Evaluation of ovulation and corpus luteum function using measurements of plasma progesterone. Obstet Gynecol44:522, 1974