Chung H. Wu

Monitoring of Ovulation Induction

The plasma hormonal patterns of the normal menstrual cycle have been reviewed. A consistent cyclic pattern of plasma hormone levels is observed in LH, FSH, estrogens, and progestins in the menstrual cycle. Other plasma hormones, such as ACTH, growth hormone, TSH, and PRL, as well as androgens and corticosteroids, fluctuate throughout the menstrual cycle without any consistent pattern during the ovulatory cycle. FSH, LH, E2, E1, P, T, and A levels during the induced ovulatory cycle are presneted for comparison. In the gonadotropin-induced ovulatory cycle most hormones behave in a manner similar to that in the normal ovulatory cycle, except for FSH levels, which rise continuously throughout the follicular phase of the cycle. Following ovulation in the gonadotropin-induced cycle, T rises above normal levels. Early in the clomiphene-induced ovulatory cycle, unlike the normal cycle, LH is distinctly elevated. Levels of both LH and FSH in the rest of the cycle simulate those in the normal cycle. However, T and A levels rise from the very beginning of clomiphene therapy and continue to rise throughout the clomiphene-induced ovulatory cycle. Levels of E and P are higher than in the normal ovulatory cycle, but a similar pattern is preserved. Because of the potential dangers of gonadotropin therapy, monitoring by frequent examination and laboratory tests is required. E monitoring is mandatory to evaluate follicular maturation, to time hCG administration, and to minimize hyperstimulation. Cervical mucus is an unreliable parameter for monitoring gonadotropin therapy alone. In addition to cervical mucus, plasma or urinary E should be monitored regularly. Clomiphene therapy is less dangerous than gonadotropin therapy. Because of its lesser risk, monitoring is rarely performed during clomiphene use. An active monitoring approach has been described. While this approach may not necessarily improve the outcome of clomiphene therapy, it may hasten the process of selecting the appropriate dose. Although other ovulation-inducing agents are available, their use is rarely associated with serious medical complications, and monitoring would seem unnecessary.

Estrogen-androgen balance in hirsutism.

Random blood samples were obtained from a group of patients having oligomenorrhea or secondary amenorrhea, who responded to progesterone with uterine withdrawal bleeding, associated with hirsutism (N = 35) or not associated with hirsutism (N = 9). A few blood samples were obtained during the midfollicular phase of normal cycles in age-matched normal females (N = 10) as controls for comparison. Plasma gonadotropins (follicle-stimulating hormone and luteinizing hormone [LH]) and steroid hormones including testosterone (T), androstenedione (A), estradiol (E 2 ), estrone (E 1 ), and progesterone (P) were quantitated by radioimmunoassay. The percentage of free fraction of E 2 and T was determined by equilibrium dialysis at 37° C, and the percentage of T-E 2 -binding globulin (TeBG)-bound fraction of E 2 and T was estimated by the specific steroid displacement-charcoal adsorption technique. The binding capacity of plasma TeBG was measured by the modified Scatchard plot technique. The E 2 :T ratios of concentrations and the binding parameters were also evaluated. The weight (but not height) of hirsute females was significantly higher than that of normal females. Plasma LH, T, A, and E 1 levels were significantly elevated in hirsute females. Plasma T concentrations, including free, index, and total, correlated positively with degree of hirsutism. E 2 :T ratios of concentration also suggested a similar, but negative, correlation. The percentage of free E 2 increased more than the percentage of free T when the percentage of TeBG-bound E 2 decreased more than the percentage of TeBG-bound T in hirsute females. The E 2 :T ratios of the percentage of free and TeBG-bound fractions did not show any correlation with degree of hirsutism. The T-binding capacity of plasma TeBG decreased in hirsute females and was also correlated significantly with degree of hirsutism. The elevated plasma T concentrations (including free, index, and total concentrations) in hirsute females overlapped significantly with that of normal females, thus they failed to discriminate each other.

Free and protein-bound steroids in amniotic fluid of midpregnancy

Ninety-seven amniotic fluid (AF) specimens, 67 with male fetuses and 30 with female fetuses, were obtained by amniocentesis at 14 to 18 weeks of gestation for analysis of free and protein-bound estrone (E1), estradiol (E2), androstenedione (A), testosterone (T), and progesterone (P). Ten maternal plasma (MP) samples of comparable gestational age were analyzed for the same free and protein-bound steroids. Significantly lower total E1, E2, A, and T, but not P, levels were found in AF when compared to MP. The percentage of free steroids was higher in AF than in MP, while the percentage of specific protein-bound steroids was lower in the AF than in MP. Free (unbound) steroid levels of E1 and P were higher in AF than in MP, whereas levels of E2 were lower in AF than in MP. The free A and T levels in MP were lower than in AF with male fetuses, yet higher than in AF with female fetuses. Possible biologic activity of steroids in this fluid may depend on the dynamic balance between the free, the specific protein-bound, and the nonspecific protein-bound steroids.

Search for arteriovenous shunts in the genital tract of the pseudopregnant rabbit.

Introduction. The blood flow within an endocrine gland plays an essential role in the control of its physiological activities. Some of the complex hemodynamics changes of the ovary have been described during the preovulatory period ( 1 ), pseudo-pregnancy ( 2 , 3 ), and pregnancy ( 4 ). The mechanisms that regulate these changes are not clear, but hormones ( 5 , 6 ) and amines have been implicated in circulatory control ( 7 ). The luteolytic process is characterized by a remarkable decline in ovarian blood flow ( 4 ) and progesterone secretion ( 8 ). The drop in blood flow to the corpus luteum has been attributed to the presence of arteriovenous shunts which would divert blood flow from the corpus luteum ( 9 ). In this report we present evidence indicating that, in the pseudopregnant rabbit, no demonstrable arteriovenous shunts are found in the ovary. Materials and methods. Mature New Zealand White rabbits, 3-4 kg in weight, were kept in individual cages for 3 weeks prior to use. Blood flow determinations were carried out 6, 12, and 18 days after iv administration of 100 IU of hCG. Analgesia was induced with Innovar (0.2 mg/kg) administered intramuscularly. Both femoral arteries were catheterized with a poly vinyl tube (PE. 60, Clay-Adams, N.J.). The right catheter was advanced until its tip was about 3 cm below the diaphragm. This catheter was used for the administration of radioactive microspheres. The left femoral catheter was advanced about 2 cm into the artery and connected to a Harvard pump. Each animal received approximately 1,500,000 micro-spheres, 15 ± 5-μM diameter, labeled with St85 and 400,000 microspheres, 50 ± 5-μm diameter, labeled with CE141 (3M Company, St. Paul, Minn.). The spheres were suspended in 0.8 ml of 10% dextran in physiologic saline, mixed well, and injected immediately through the right femoral catheter.

Estrogen-Androgen Balance in Anovulation

The balance of estradiol (E2) and testosterone (T) in 15 anovulatory patients was evaluated by measuring the daily plasma concentration of E2 and T, and their free and protein-bound fractions for a 3- to 4-week period. Similar daily plasma E2 and T data were obtained from five normal ovulatory cycles as a control group. The daily concentration of the free, non-testosterone-estradiol-binding globulin (TeBG)-bound (index), and total E2 fluctuated in a wider range than that of the T in the ovulatory as well as in the anovulatory cycles. The percentage of free (%F) and TeBG-bound (%TeBG) fractions of both E2 and T were relatively constant. The concentration of the free, index, and total E2 and T showed a parallel pattern even in anovulatory cycles. An increased %F fraction associated with a decreased %TeBG fraction of E2 and T was observed in anovulatory patients who were hypo- or normoestrogenic; however, an opposite shifting of these two fractions was observed in anovulatory patients who were severely hypoestrogenic. In a hyperestrogen-normoandrogenic state, there was a significant increase in the binding of E2 and T. The daily binding capacity of plasma TeBG revealed a greater fluctuation than the binding fractions, and it decreased in anovulatory patients, especially in the hyperandrogenic state. E2:T ratio of concentration showed a curve-linear relationship to %F, %TeBG, and binding capacity of sex steroids.

Plasma Hormone Profile in Anovulation

Daily plasma hormones, including luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, androstenedione, and testosterone (T), were measured in 16 anovulatory patients for a span of 3 to 4 weeks. The clinical diagnoses in this group of patients included the following: anovulation-eumenorrhea (n = 5), anovulation-polymenorrhea (n = 1), anovulation-oligomenorrhea (n = 3), congenital adrenal hyperplasia (n = 1), polycystic ovarian disease (n = 4), severe hypothalamic amenorrhea (n = 1), and postpartum amenorrhea-galactorrhea (n = 1). Follicular activity was evident in polymenorrheic and oligomenorrheic patients, and menstruation occurred in these patients following estrogen withdrawal. No follicular maturation was noted in the group of patients with anovulation-eumenorrhea, and menstruation in these patients was considered breakthrough bleeding. Low FSH levels were observed in anovulatory patients with eumenorrhea, polymenorrhea, and oligomenorrhea. Significantly high LH values were noted in both classic and non-classic polycystic ovarian disease. Extremely low E1 and E2 levels were found in patients with severe hypothalamic amenorrhea and postpartum amenorrhea-galactorrhea. Slightly elevated progesterone levels were observed in polymenorrheic and oligomenorrheic patients prior to menstruation; this was frequently associated with an LH surge or elevation. Elevated T levels were consistently associated with hirsutism but not with obesity.