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PubMed1991

Hyperandrogenism: new insights into diagnosis and therapy.

Many different disease processes can result in a phenotype of hirsutism, anovulation, and oligomenorrhea or amenorrhea. An important goal of reproductive endocrinologists is to identify specific genetic diseases that can produce the hyperandrogenic phenotype. Two genetic disorders that can result in the hyperandrogenic phenotype are 1) mutations in the 21-hydroxylase gene (adrenal hyperplasia), and 2) mutations in the insulin receptor gene (the syndrome of hyperandrogenism-insulin resistance and acanthosis nigricans). The identification of these two genetic causes of hyperandrogenism provides the opportunity to investigate new approaches to prenatal diagnosis and therapy, genetic analysis of pedigrees, and innovative forms of therapy.

Acanthosis Nigricans↗

PubMed1991

Ovulatory dysfunction during continuous administration of low-dose levonorgestrel by subdermal implants.

OBJECTIVE: To study the endocrinologic profile of regularly menstruating users of levonorgestrel subdermal implants. DESIGN: Observational, prospective, case-controlled comparative study. SETTING: The Family Planning Clinic of PROFAMILIA, in Santo Domingo, Dominican Republic. PATIENTS, PARTICIPANTS: Thirty one regularly cycling Norplant users and 12 nonhormonal contraceptors who volunteered to participate. INTERVENTIONS: Norplant contraceptive implants were inserted in 31 subjects between 13 and 77 months before this study. MAIN OUTCOME MEASURES: Follicle-stimulating hormone, luteinizing hormone, estradiol (E2), and progesterone (P) were serially assayed for one menstrual cycle. RESULTS: Almost half of the cycles among Norplant users were anovulatory; all the rest (55%) had some form of dysfunction: diminished gonadotropin surge, luteal phase insufficiency (low P levels and shortened luteal phase), and E2 profiles different from normal controls. CONCLUSIONS: Anovulation is clearly one of the main mechanisms of action of Norplant, but even in presumptive ovulatory cycles, the dysfunctions described possibly contribute to the high contraceptive effectiveness of Norplant.

Adult↗

PubMed1990

Methods of ovulation induction.

The results of ovulation induction in patients with ovulatory dysfunction were reviewed for a one year period. Eighty-six women were assigned to four groups: secondary amenorrhea, anovulation, oligo-ovulation, and luteal phase defect/short luteal phase (LPD). All patients were monitored with basal body temperature (BBT) graph, postcoital testing, and ultrasonic scanning of ovarian follicles. All patients received therapy with clomiphene citrate (CC) for a minimum of four cycles and 13 patients conceived. Fifty patients were offered additional therapy with human menopausal gonadotropins (HMG-HCG). Seventeen completed a minimum of four cycles, and 13 conceived. The number of CC-treated patients with poor mucus quality in the face of adequate follicular development was 24, or 48%. The overwhelming problem with ovulation induction when CC failed was the large number of patients who dropped out of therapy, 48%. In summary, close monitoring during ovulation induction to confirm ovulation, and assess mucus quality and luteal function allow detection and correction of inadequate response. Induction of ovulation can be highly successful if patients can follow through and complete protocols of therapy.

Adult↗

PubMed1990

[Clinical and endocrinologic aspects of treatment with pure FSH. A report of experiences].

Ovarian stimulation with pure urinary FSH (Fertinorm, Serono Freiburg, FRG) shows therapeutic efficacy in patients with chronic clomiphene-resistant anovulation and elevated androgen levels. In case of unsatisfactory ovarian response the rate of success can be improved by adding HMG. 20 patients were stimulated for a total of 36 cycles. Cycle monitoring was performed by transbdominal ultrasound and cervical mucus evaluation. Hormone determination (E2, LH, FSH, prolactin, testosterone, DHEAS) was carried out retrospectively. In 17 cycles HMG was added because of insufficient follicle maturation. Upon achieving a dominant follicle with a diameter of more than 1.6 cm (25 cycles, 14 of those with FSH stimulation only) HCG was applied for induction of ovulation. In 22 cycles ovulation occurred. 7 of those revealed sings of luteal phase deficiency. In anovulatory cycles (n = 3) there was a discrepancy between sonography and E2-levels. Premature increase in LH, partly with subsequent luteinization of follicles was observed in 7 of all 36 cycles (19.4%), 2 of those under sole FSH-stimulation. The number of dominant follicles on the day of HCG-application was 1.40 +/- 1.06 (n = 15) in cycles with FSH alone and 2.09 +/- 1.76 (n = 11) in cycles with additional HMG. Hyperstimulation (more than 4 leading follicles) was induced in 9 cycles (5 cycles with FSH only). In 7 (4) cases HCG had to be cancelled. Polyfollicular ovarian reaction and premature increase in LH preferentially occurred in cycles with high basel levels of LH and elevated LH/FSH-ratio.

Adult↗

PubMed1990

[Breast diseases in patients with hyperandrogenism].

The study has been undertaken in 40 women with excessive androgen levels in the age range of 22 to 38 years. Various types of mastopathy were found in 34 and fatty degeneration of the glandular tissue in 6 women. On the basis of clinical and laboratory studies, the patients were assigned to 3 groups: ovarian hyperandrogenism, adrenal and ovarian-adrenal hyperandrogenism. Breast hyperplasia was seen in all groups, but adenofibrosis occurred in groups I and III at a 2-2.5-fold higher rate as compared with group II. The patients with hyperandrogenism, anovulation, increased body mass index, low hirsute number and polycystic ovaries were at the highest risk of dyshormonal mammary hyperplasia. An adequate therapeutic approach was suggested for mastopathies in hyperandrogenic patients.

Adrenal Gland Diseases↗

PubMed1989

[Sex hormones and the skin].

The relationship between sex hormones and the skin is increasingly considered to be very important. The skin has appropriately been called "A peripheral endocrine gland". In this review some aspects of the cutaneous metabolism of oestrogens, progestogens and particularly androgens are analyzed. Production of skin collagen is markedly enhanced by oestrogens. Progestogens with strong androgenic activity and especially androgens have a powerful stimulating action on all skin elements particularly the epidermis and the dermis the sebaceous glands and the hair. The skin manifestations of hyperandrogenism and disturbances of reproductive functions such as anovulation, oligoamenorrhoea and polycystic ovarian disease are usually the consequences of three main aetiopathogenic factors: the first is an abnormality of GnRH pulsatility related to central nervous system dysfunction and seemingly mediated by an increase in beta Endorphin, possibly related to some extent to changes in body weight and hyperinsulinism. The second aetiopathogenic approach is hyperaestronaemia secondary to obesity. Finally adrenal hyperandrogenism caused by different types of congenital adrenal hyperplasia or by increased sensitivity to ACTH may be implicated in these various clinical manifestations.

Amenorrhea↗

PubMed1989

Hyperandrogenism in infertility.

Hyperandrogenism, whether of ovarian or adrenal etiology, can be associated with impairment of folliculogenesis, resulting in anovulation. Various therapeutic modalities can be utilized to reestablish ovulation, including correction of the underlying pathophysiology, the use of fertility-promoting drugs and surgery.

Androgens↗

PubMed1989

[State of the endometrium in patients with female genital tuberculosis according to biopsy data].

Comparison of the clinicoanatomic materials relating to 430 female patients with genital tuberculosis showed that 56 per cent of the patients had hormonal disorders among which deficiency of the cycle phase II or anovulation predominated. Variants of glandular cystic hyperplasia were the most frequent morphological equivalents of the hormonal disorders. In the morphological characteristics of the glandular cystic hyperplasia variants there were no differences in the level of gland and stroma maturity in the groups under observation. The use of the method of informative entropy in estimation of endometrium pathology provided objective morphological diagnosis and extended the diagnostic possibilities due to detecting hormonal disorders at the subclinical level which was especially important for early correction of the hormonal disorders.

Adult↗

PubMed1989

[Oligomenorrhea syndrome in infertile patients].

The paper presents the results of comprehensive studies of 100 infertile patients with oligomenorrhea. Familial predisposition to the impairments in the menstrual and reproductive functions was established as was a high rate of primary infertility and pregnancy wastage. Ninety per cent of the patients demonstrated ovarian dysfunction from the puberty, refractory anovulation was registered in the majority of the patients (70 per cent), intermittent in 22 and persistent ovulation only in 8 per cent of the examinees. Clinical and laboratory investigations confirmed hyperandrogenism in 80 per cent and hyperprolactinemia in 28 per cent of the patients. Laparoscopy demonstrated a high incidence of ovarian polycystosis (57 per cent), inflammatory genital changes (47 per cent), uterine myoma (7 per cent), and endometriosis of the external genitalia (7 per cent). There was no evidence of correlation between the content of plasma hormones, ovulatory disorders and endoscopic findings.

Adult↗

PubMedDate not supplied

Ovulation monitored by serum 17 beta-estradiol and ultrasound: differential ovarian response to human gonadotropins in various anovulatory states.

Ovulation induction with human gonadotropins (hMG or pFSH and hCG) was simultaneously monitored with daily serum 17 beta-estradiol measurements and ultrasound in 38 infertile women. They were subgrouped as follows: A, hypogonadotropic hypogonadism (n. 7); B, polycystic ovary syndrome (n. 13); C, non-PCO chronic anovulation (n. 6); D, unexplained infertility (n. 12). The dose of hMG and the duration of therapy were assessed individually depending on the results of the monitoring when serum estradiol concentration was 500-1500 pg/ml and/or ultrasound showed of a follicle of at least 18 mm, hMG was stopped and hCG was administered 36 hours later. Ovulation was obtained in 61 cases and pregnancy occurred in 12 women out of 64 monitored cycles. The highest pregnancy rate was observed in hypogonadotropic hypogonadism; this group also required the greatest total dose of hMG to obtain ovulation. We confirm that women with PCOS are at increased risk with this therapy, since 5 subjects in our series showed signs of ovarian hyperstimulation in spite of the lowest total dose of FSH administered to this group. We conclude that anovulatory states of various origin are associated with different ovarian sensitivity.

Adult↗

PubMed1978

Clinical studies with d-Trp 6-luteinizing hormone-releasing hormone in anovulatory women.

Nine anovulatory patients with hypothalamic-pituitary dysfunction were treated with d-Trp6-luteinizing hormone-releasing hormone, an analog with far greater gonadotropin-releasing activity than luteinizing hormone-releasing hormone. Four of eight patients, who were formerly unsuccessfully treated with clomiphene, human chorionic gonadotropin, and human menopausal gonadotropin, ovulated after treatment with the peptide alone or with peptide preceded by clomiphene, and three became pregnant. The ninth patient, who had amenorrhea and anovulation due to excessive loss of weight caused by anorexia nervosa, also ovulated after treatment with the analog. These results demonstrate the effectiveness of this potent analog for induction of ovulation and pregnancy and point favorably toward clinical applications.

Adult↗

PubMed1986

[Induction of ovulation using pulsatile GnRH administration to infertile females].

6 infertile women with primary or secondary amenorrhoea or anovulation, who failed to ovulate after clomiphene and HMG/HCG treatment, underwent 11 treatment cycles with pulsatile GnRH therapy using a portable pump. Normal ovulation occurred in 9 out of 11 treatment cycles; the luteal phase was normal in 6 cycles. One woman conceived in the second treatment cycle.

Adult↗

PubMedDate not supplied

The endocervical smear as a simple and quick method for the determination of ovulation.

The endocervix undergoes cyclic changes in every menstrual cycle, as reflected by the rheologic properties of the cervical mucus. A study was therefore undertaken to establish whether there were any morphologic changes in the endocervical columnar cells, as seen in the endocervical smears, that could be correlated with ovulation and anovulation. An endocervical smear was collected in the luteal phase of the cycle from patients in whom an endometrial biopsy or D & C was being done as a part of an infertility investigation. A significant correlation was observed between the endocervical smear interpretation and the endometrial histology as to whether the cycle was ovulatory or anovulatory.

Adult↗

PubMed1985

Ovulatory disorders in women with polycystic ovary syndrome.

With the use of pelvic ultrasound imaging we have found that more than half of the women presenting to our clinic with ovulatory disturbances have polycystic ovaries. As a group hirsutism is common, the serum LH, the LH:FSH ratio and serum androgen levels are higher than in other groups of patients with anovulation, but many of the women we studied were non-hirsute and had normal levels of these hormones. The aetiology of PCOS remains obscure and there is probably more than one cause. Disturbance of hypothalamic/pituitary, ovarian or adrenal function could all result in the development of polycystic ovaries. Our own data, based on pelvic ultrasound and measurement of serum androgen levels, suggest that an ovarian abnormality, other than the obvious morphological one, may be identified in most women although this does not prove (except perhaps in those women with unilateral PCOS) that the ovary is the primary site of the disturbance. Management of ovulatory disturbances includes symptomatic treatment of dysfunctional uterine bleeding and induction of ovulation. Although the ovulation rate following clomiphene is quoted as about 75%, this is probably an overestimate; less than half the 'ovulators' become pregnant and in those who do there is a high risk of early pregnancy loss. Induction of ovulation in clomiphene non-responders remains a difficult problem. The results of ovarian wedge resection are variable and any beneficial effect is short-lived with the risk of long-term infertility due to pelvic adhesions. Laparoscopic electrocautery may be a useful alternative, but it is too early to assess this form of treatment. Of the medical methods of ovulation induction in clomiphene non-responders, two methods have emerged as being highly promising: the first is administration of HMG following suppression of the pituitary by an LH-RH analogue; so far only a very small number of patients have been treated. The second is low-dose FSH. Initial studies, including our own, have shown a high incidence of ovulation and a pregnancy rate of 50%.

Androgens↗

PubMed1985

Serum carotene levels in female long-distance runners.

Hypercarotenemia has been associated with anorexia nervosa and hypothalamic amenorrhea. With the emergence of a spectrum of menstrual dysfunction, including anovulation in women runners, the hypothesis of hypothalamic amenorrhea in these patients has been formulated. Other authors have proposed exercise-associated amenorrhea to be distinct from hypothalamic amenorrhea based on endocrine profiles. Using carotene as an index test of hypothalamic amenorrhea, we have studied female long-distance runners (greater than 25 miles/week) and have found no difference in the carotene levels between ovulatory (midfollicular) and anovulatory runners. These data support other evidence that exercise-associated amenorrhea is distinct from hypothalamic amenorrhea.

Adult↗

PubMed1981

Neuroendocrine control of human ovulation.

Ovulation, defined as the release of a mature oocyte from a ruptured Graafian follicle at the surface of the ovary, is the culmination of the process of follicular maturation. The latter is under the synergistic influence of the pituitary gonadotropins, follicle stimulating hormone (FSH), and luteinizing hormone (LH), the secretion of which is, in turn, stimulated by the hypothalamic decapeptide, LH-releasing hormone (LH-RH). There is a complex interrelationship between the ovarian steroid hormones, estradiol and progesterone, and the gonadotropins, with estradiol exerting both negative and positive feedback effects on the hypothalamo-pituitary unit. Ovulation is triggered by a surge of LH which results from at least two estradiol-induced phenomena, increased hypothalamic production of LH-RH and increased pituitary responsiveness to releasing hormone. Ovulation occurs 16-17 hours following the LH peak and the probability of conception following an act of coitus appears to be maximal 1-2 days prior to ovulation itself. States of anovulation are frequently seen in association with hyperprolactinemia whereas ovulation may be delayed under a variety of circumstances.

Adult↗

PubMed1982

[Prolactin, bromocriptine and gonadic function in women: recent discoveries. I. The physiology of prolactin and the physiopathology and diagnosis of hyperprolactinaemias].

Estrogens are involved in the regulation of the secretion and release of prolactin, and so are a large number of neurotransmitters and neuropeptides. This explains why the circulating level of prolactin is very labile. Most of these elements work by bringing about small changes in the tone of the dopaminergic inhibitor system, which is the principal controlling factor for this hormone. Most hyperprolactinaemias of a pathological nature seem to be the result of a failure of this dopaminergic inhibiting system. Prolactin has a rudimentary luteotrophic function, but it does act as an inhibitor of female gonadic function as soon as the circulating level reaches about 30 ng/ml, and it exerts its effects at two levels--the ovarian and the hypothalamic. Estimating levels of prolactin should be carried out according to a strict protocol so that many causes of non-pathological rise can be excluded. Hyperprolactinaemia should be sought whenever anovulation is found whether it is accompanied by galactorrhoea or not. Certain cases of hyperprolactinaemia are secondary to different types of aetiology which have to be searched for. When confronted with a case of primary hyperprolactinaemia the search should be towards diagnosis of a pituitary adenoma, which is often present although very small. Two examinations that are of most value to diagnose this condition are standard X-rays of the pituitary fossa and scanning tomography.

Adenoma↗

PubMed1978

Estrogen excretion patterns in induced ovulation.

Observation of response to gonadotropins in the treatment of anovulation has allowed us to define the estrogen excretion pattern which leads to a successful single pregnancy. The typical pattern shows a low pretreatment urinary total estrogen excretion; treatment with gonadotropins, of human pituitary origin, is continued for about 14 days. There is a predictable rate of rise of preovulatory estrogen excretion (30 microgram/24 hr2). Human choronic gonadotropin--about 4000 IU--should be given when an estrogen excretion of 75-100 microgram/24 hr has been obtained. The use of this pattern of ovarian response is put forward as a useful guide in the planning of gonadotropin therapy.

Anovulation↗