Jacquelyn S. Loughlin

A conservative approach to the management of uterine leiomyoma: Pituitary desensitization by a luteinizing hormone- releasing hormone analogue

Uterine leiomyoma is the most common solid tumor of the female genital tract and may cause heavy menometrorrhagia and infertility. Uterine myomectomy is not always feasible and total hysterectomy may be necessaryin young women who have not yet completed their families. Herein we report the regression of a presumed uterine leiomyoma induced by long-term treatment with a long-acting luteinizing hormone-releasing hormone (LHRH) agonist, which was administered to suppress ovarian estrogen secretion. sent from the patient. Metrorrhagia subsided within 48 hours from the initiation of treatment, at the time of the rapidly rising estradiol levels that characterize the agonist phase of LHRH, administration (Fig. 2). Another episode of uterine bleeding occurred 13 days after the beginning of therapy, coincident with suppression of serum estradiol to prepubertal levels. During the first 2 months of therapy the patient reported only minor episodes of vagina1 bleeding, usually lasting no longer than 1 day. No further bleeding occurred after the eighth week of therapy, and the hemoglobin level rose steadily from a pretherapy value of 7.4 gm/dl to 12.8 gmldl within 60 days. Plasma estradiol levels became undetectable (~20 pg/mI) during the third week (Fig. 2) and the patient noted the onset of hot flashes shortly thereafter. At 8 weeks of treatment the leiomyoma had decreased to 5 by 5 by 4 cm according to ultrasound examination and a further reduction to 4 by 4 by 4 cm had occurred by the twelfth week (Fig. 1, B). At 15 weeks the size of the mass was noted to be unchanged at 4by4by4cm.

Long-term treatment of central precocious puberty with a long-acting analogue of luteinizing hormone-releasing hormone. Effects on somatic growth and skeletal maturation

Abstract The gonadotropin-releasing hormone–like agonist d-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (±S.E.M.) of 9.35±0.64 cm per year during the 19 months before treatment to 4.58±0.60 cm per year during treatment (P<0.001). Bone age advanced a mean of 9.4 ±2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P<0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa t...

Puberty without gonadotropins: a unique mechanism of sexual development

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Bilateral compartment syndrome after a long gynecologicoperation in the lithotomy position

Compartment syndrome occurred after a tubal anastomosis in a prolonged lithotomy position. This syndrome carries the risk of permanent neuromuscular and kidney damage. The pathophysiologic features of the syndrome are reviewed. Specific guidelines for the prevention and management of this syndrome in patients undergoing gynecologic procedures are presented.

Effects of chronic luteinizing hormone-releasing hormone administration on gonadotropin dynamics of adult male rats.

Abstract The studies reported herein were conducted to determine the sequential effects of chronic luteinizing hormone-releasing hormone (LHRH) or D-Trp6-Pro9-NEt-LHRH (LHRHa) administration on LH, FSH, and T dynamics. Adult male rats (n = 6/group) were injected subcutaneously with 1 μg of LHRH or LHRHa once daily at 8:00 am for 1 through 7 days. The rats were decapitated at various times postinjection and their blood, pituitaries, and testes collected. When measured 24 hr after each injection, significant (P ≤ 0.01) decreases were observed in concentrations of serum T and pituitary LH and FSH as well as testicular volume; whereas basal serum concentrations of LH and FSH were significantly (P ≤ 0.01) elevated from Days 3 through 7 in both LHRH and LHRHa-treated rats. LH was secreted in a large single peak 1 hr after each LHRH injection, increasing 54-fold above preinjection concentrations on Day 1 and lessening to a 34-fold increase on Days 3 through 7. The magnitude of the FSH response was not altered with chronic LHRH treatment. The peak responses of both LH and FSH were blunted with LHRHa treatment. When rats were castrated after 5 days of LHRH treatment, the castration-induced rise in serum FSH concentration was normal, whereas the LH rise was delayed and blunted. These data indicate that: (1) Chronic treatment with LHRH or LHRHa results in elevated basal serum gonadotropin concentrations and reduced basal serum testosterone concentrations and pituitary LH and FSH concentrations. (2) Chronic treatment with LHRH reduces the serum LH response (but not the FSH response) to subsequent LHRH injections. Furthermore, chronic treatment with essentially an equimolar dose of a potent LHRH agonist (d-Trp6-Pro9-NEt-LHRH) blunts both the LH and the FSH response to subsequent LHRH agonist injections. Furthermore, chronic treatment with essentially an equimolar dose of a potent LHRH agonist (D-Trp6-Pro9-NEt-LHRH) blunts both the LH and the FSH response to subsequent LHRH agonist injections. (3) FSH responses to castration are not altered by chronic LHRH treatment, whereas LH responses to castration are decreased. Treatment with a potent LHRH agonist prevents the normal rise in serum LH and FSH concentrations following castration.

Testosterone, a Follicular Regulator: Key to Anovulation

To study the interrelationships of steroids within the follicle, combined 6-h infusions of [3H]dehydroepiandrosterone sulfate and [14C] testosterone ([14C]T) were performed in four normal women treated with menotropins who were undergoing medically indicated surgery. The concentrations of tracer and/or nonisotopic dehydroepiandrosterone sulfate, androst-5-ene-3 beta,17 beta-diol sulfate, androst-5-ene-3 beta,17 beta-diol, dehydroepiandrosterone, androstenedione, T, dihydrotestosterone, estrone (E1), and estradiol (E2) were determined in arterial and venous blood and follicular fluid. The log-transformed product/precursor ratio of [3H]dihydrotestosterone/[3H]T in follicular fluid was negatively correlated with the log-transformed follicular concentrations of E1 (P = 0.01) and E2 (P = 0.02), suggesting a reciprocal relationship between 5 alpha-reductase and follicular E1 and E2. E2 and T were positively correlated in follicular fluid (r = 0.84; P = 0.0003), suggesting a stimulatory action of follicular T on aromatase. These findings along with extensive published data suggest that follicular T functions as a follicular regulator, enhancing follicular aromatase activity when adequate amounts of FSH are available. These conclusions have important implications with regard to mechanisms for selecting the dominant follicle and producing atresia in the remaining cohort of follicles, and they describe a final common path in the pathophysiology of anovulation.

Long-Term Treatment of Central Precocious Puberty with a Long-Acting Analogue of Luteinizing Hormone-Releasing Hormone. Effects on Somatic Growth and Skeletal Maturation

The gonadotropin-releasing hormone-like agonist D-Trp6-Pro9-NEt-LHRH (LHRHa) has been shown to induce a reversible short-term suppression of gonadotropins and gonadal steroids in patients with central precocious puberty. Since accelerated statural growth and bone maturation are clinical features of precocity not well controlled by conventional therapies, we examined the effects of prolonged LHRHa therapy for 18 consecutive months on growth and skeletal maturation in nine girls with neurogenic or idiopathic precocious puberty. Suppression of gonadotropin pulsations and gonadal steroids was maintained in all subjects. Growth velocity fell from a mean rate (+/- S.E.M.) of 9.35 +/- 0.64 cm per year during the 19 months before treatment to 4.58 +/- 0.60 cm per year during treatment (P less than 0.001). Bone age advanced a mean of 9.4 +/- 2.3 months during treatment. These changes resulted in a mean increase of 3.3 cm in predicted height (P less than 0.01). Complete suppression of the pituitary-gonadal axis can be maintained by LHRHa therapy, resulting in slowing of excessively rapid growth and skeletal maturation and in increased predicted adult height in girls with precocious puberty.