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Objective To compare two dosages of oral micronized progesterone (P) and placebo for withdrawal bleeding and side effects. Design Prospective, randomized, double-blind. Setting Academic institution. Participants: Out of 190 screened with oligomenorrhea/amenorrhea, 60 who qualified completed the study. Interventions A 10-day course of (1) oral micronized P 300mg, (2) oral micronized P 200mg, or (3) placebo. Main Outcome Measures Withdrawal bleeding, side effects, and changes in lipids. Endogenous estradiol (E 2 ) concentrations at baseline and P concentrations during treatment were correlated with bleeding response. Results Withdrawal bleeding occurred in 90% of women taking 300mg, 58% of women taking 200mg, and 29% of women taking placebo ( P P =not significant). Lipid concentrations were unchanged. Endogenous E 2 and treatment P concentrations were of limited predictive value for withdrawal bleeding. Conclusions Progesterone 300mg induced significantly more withdrawal bleeding than placebo, with similar side effects. Bleeding response cannot be predicted reliably from E 2 and P concentrations.

Objective To report an unusual case of secondary amenorrhea in a 17-year-old adolescent with normal sexual development who proved to have a karyotype 46,XX/46,X,+ringX/47,XX,+ringX. Design Case report. Setting Hospital, tertiary level of clinical endocrine care. Patient(s) A 17-year-old patient with secondary amenorrhea and normal sexual characteristics with no stigmata of Turner syndrome. Intervention(s) Clinical history, hormonal markers, cytogenetic analysis. Main Outcome Measure(s) Cytogenetic analysis by G-banding technique, multicolor fluorescence in situ hybridization, and multicolor banding analysis on peripheral blood lymphocytes. Result(s) The presence of mosaicism in 12% of metaphases indicating a ring X chromosome with one or two normal X chromosomes, forming a karyotype 46,XX/46,X, +ringX/47,XX,+ringX. Conclusion(s) Our findings indicate the necessity for cytogenetic studies in certain cases of amenorrhea. This is a very rare karyotype in patients with secondary amenorrhea.

Objective: To determine whether the insertion of a copper intrauterine device can restore regular menses in patients with functional secondary amenorrhea. Design: Prospective, observational study. Setting: Clinical practices. Patient(s): Forty-eight volunteers with functional secondary amenorrhea. Intervention(s): Insertion of a copper intrauterine device. Main Outcome Measure(s): Restoration of menses. Result(s): In 40 patients, regular menses were restored within a few weeks after insertion of the device. Normal menses were maintained as long as the copper intrauterine device remained in place. After removal of the device, normal menses persisted for 1 year. Conclusion(s): Insertion of a copper intrauterine device restores regular menses in women with functional secondary amenorrhea. The mechanism of action of the device probably is related to the release of prostaglandins from the endometrium.

Objective To review the diagnostic possibilities that exists when the workup of amenorrhea reveals an isolated LH elevation; and to examine the effect of inhibin B on LH levels in vivo. Design Case report. Setting University hospital. Patient(s) A 20-year-old woman presented with secondary amenorrhea. Her FSH measurement was low, and the LH level was elevated. The recognition that this was an unusual pattern led to the diagnosis of a rare but very treatable inhibin B–producing thecoma, despite the fact that results on the initial pelvic ultrasound examination performed 10 months after presentation of amenorrhea were relatively unremarkable. Intervention(s) Surgical removal of an ovarian thecoma. Main Outcome Measure(s) Gonadotropins, E 2 , inhibin B, menstrual bleeding, and fertility. Result(s) Removal of the ovarian thecoma resulted in a normalization of FSH, LH, and inhibin B levels and a return of spontaneous menses 28 days later. Pregnancy occurred with the third postoperative menstrual cycle, followed by the delivery of a healthy full-term girl. Conclusion(s) Inhibin B–producing sex cord granolosa–stromal cell tumors should be considered in women who present with amenorrhea with isolated LH elevations, even in the setting of a previously normal pelvic ultrasound report. Diagnostic considerations that arise in the workup of amenorrhea when there is an isolated elevation in LH that is accompanied by normal or low FSH levels are reviewed. This rare clinical presentation provides the opportunity to observe the impact of inhibin B on gonadotropins in vivo.

The eating and exercise history of women with secondary amenorrhea and failure of ovulation using CC was studied in 14 consecutive women on a GnRH-a program. All had a history of an eating or exercise disorder. At the time of the interview, 7 women continued to have an eating or exercise disorder. There were 15 pregnancies (12 women) with 12 live births, of which 4 weighed less than 2,500 g. Infertility specialists should inquire routinely about a woman's body weight and eating and exercise behaviors, and consider treatment for these before prescribing drugs to induce ovulation.

Thirty women with secondary amenorrhea and hyperprolactinemia were studied; galactorrhea was present in 25 of them, and 18 were infertile. Serum prolactin (PRL) levels were high in all cases, between 26 and 120 ng/ml. All women were treated with bromocriptine in increasing doses from 2.5 to 5.0 or 7.5 mg daily, according to the response obtained, for 4 months. In 27 patients a PRL determination was performed during treatment; values returned to normal (up to 20 ng/ml) in 23 women and remained high in 4. Galactorrhea disappeared in 21 of 25 women. Ovulatory menses were re-established in 17 patients (56.6%). Seven women became pregnant (38.8%), one of them after bromocriptine and clomiphene were given simultaneously in the same cycle. According to our results and a literature review the following conclusions may be drawn: (1) bromocriptine is a useful therapeutic tool for re-establishing menstruation and inducing ovulation in patients with the hyperprolactinemic-amenorrhea syndrome; (2) the association of bromocriptine and clomiphene could be the next step in the treatment of patients who fail to ovulate with bromocriptine alone.

Twelve women of normal weight (ages 17 to 36 years) with scanty menstrual bleeding were studied. They had no signs of virilization, gynecologic or endocrine pathology, or past history of hormonal treatment. Five women (group 1) experienced withdrawal bleeding after a 3-day course of chlormadinone acetate (2 mg/day) and the other seven did not (group 2). Daily venous blood samples were obtained 10 to 15 days afterward for 5 consecutive days of no treatment (control period) and during the next 5 days while the women received paramethasone acetate (PA), 2 mg/day (treatment period). In each plasma sample the concentrations of 17beta-estradiol (E2) and luteinizing hormone (LH; LER-907) were determined. The mean plasma E2 levels in group 1 were 35 +/- 8 and 86 +/- 10 pg/ml during the control and treatment periods, respectively (P less than 0.001), and the mean plasma LH levels were 28 +/- 6 and 94 +/- 34 ng/ml, respectively (P less than 0.001). No significant changes in plasma E2 and LH levels were observed in group 2 in either period. During the control period, the plasma E2 level in group 2 (14 +/- 2 pg/ml) was lower than that in group 1 (P less than 0.01); however, plasma LH levels were similar in both groups. The administration of PA for 5 months induced monthly ovulation in group 1 but not in group 2. These data suggest that the best results are obtained in women with optimal pretreatment levels of plasma E2.

Women who exercise heavily may develop secondary amenorrhea. Since the mechanism of so-called "runner's amenorrhea" has not been conclusively established, the authors examined the occurrence of amenorrhea in one of the most intensively exercising groups of female runners in the United States (average, 70 miles/week): those women participating in the marathon trials for the 1984 Olympics. Nineteen percent of these Olympic runners were amenorrheic. When compared with eumenorrheic marathon runners, these amenorrheic runners were significantly ( P μ g/dl; P

Luteinizing hormone-releasing hormone (LH-RH), at a dose level of 10μg, was administered intravenously to 31 patients, 9 with oligomenorrhea and 22 with secondary amenorrhea. A serum luteinizing hormone level higher than 45 mIU/ml at 30 or 45 minutes after injection was considered to be a "positive response" to LH-RH. All 9 patients in the oligomenorrheic group and 11 of the 22 patients with secondary amenorrhea had a "positive" response. The patients were then treated with increasing doses of clomiphene citrate until an ovulatory dose was reached. Eight of the nine patients with oligomenorrhea ovulated with doses of up to 150mg of clomiphene daily for 5 days. Of the 11 patients in the group with secondary amenorrhea who had a "positive" response to LH-RH, 7 ovulated at a dose of 150mg (or less) of clomiphene citrate, while only 1 of the 11 patients with a "negative" response ovulated while receiving a similar dosage of clomiphene. These results suggest that a simplified LH-RH test might be of value in selecting the level of therapy for ovulation induction.

Serum estradiol (E 2 ), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels were measured in blood samples obtained prior to and at frequent intervals for 360 or 480minutes following the subcutaneous administration of gonadotropin-releasing hormone (Gn-RH) to eight normal women and nine patients with hypothalamic secondary amenorrhea. In the normal subjects given 100 μ g of Gn-RH on day 7 of the menstrual cycle, there was no significant increase in the mean E 2 concentration above basal levels. Six women with secondary amenorrhea received GnRH, 100 μ g, for 4 successive days; frequent blood samples were obtained on days 1 and 4. On day 1, the mean E 2 concentration at 360minutes was significantly greater than the mean basal level. On day 4 no significant increase in E 2 was detected, although the mean LH and FSH responses and basal E 2 level were not different from those of day 1. Four women with secondary amenorrhea received daily doses of 500 μ g of Gn-RH for 7days. Significant increases in mean serum E 2 concentration (100 to 150pg/ml) were noted at 6 and 8hours after administration on day 1 and at 8hours on day 4. No significant rise in E 2 was detected on day 7. The mean LH and FSH responses did not differ from those observed in women who received the 100- μ g dose, and there were no significant differences in responses on successive days of Gn-RH administration. The repeated daily administration of high doses of Gn-RH did not result in hormonal evidence of follicular maturation. Induction of follicular maturation in women with secondary amenorrhea may require frequent or continuous administration of Gn-RH to replicate more closely the sustained elevation of FSH concentration observed during the early phase of the normal menstrual cycle. Since no E 2 response was observed in normal women during the early follicular phase, ovarian responsiveness to LH and/or FSH may differ at various stages of follicular maturation.

In humans, progesterone (Po) administration has been shown capable of eliciting luteinizing hormone (LH) and prolactin surges in a good estrogenic milieu, but whether such changes induce corpus luteum function still remains controversial. We therefore proposed to explore further the second hypothesis in a placebo-controlled type of study. In patients with secondary amenorrhea and low circulating estradiol (E2) levels with or without ovaries, a 50-mg progesterone injection induced only a short and transient rise in plasma Po levels. On the other hand, a similar injection to patients with mid-to late follicular levels of circulating E2 and intact ovaries induced a surge of plasma LH and prolactin which was followed by a sustained elevation in plasma Po. Furthermore, a rise in basal body temperature accompanied by evidence of secretory endometrium was also observed in these patients. It is concluded that, in a proper endocrine milieu, progesterone administration may induce luteinization in human subjects.

Two sisters, ages 16 and 17, presented with secondary amenorrhea. In addition, primary ovarian failure, gonadal dysgenesis, and normal karyotypes were demonstrated. The most significant finding was a history of mumps, which they caught at the same time, 10 years before the onset of the amenorrhea. This disorder suggests that etiologic and environmental factors could prevail either in utero or during childhood. These patients are presented to emphasize the importance of considering gonadal dysgenesis as a differential diagnosis in patients with secondary amenorrhea, especially when the menstrual life has been a short one.