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David M Robertson

Publications and source records attributed to David M Robertson.

22 records · Page 2Linked to original sources

Variability in sperm suppression during testosterone administration to adult monkeys is related to follicle stimulating hormone suppression and not to intratesticular androgens.

Sex steroid-based male contraceptive regimens do not induce consistent azoospermia. The reason for this variable response is obscure. We used normal adult male monkeys, Macaca fascicularis (n = 9) as a model of testosterone (T)-induced gonadotropin suppression to understand the basis for variability in spermatogenic suppression during hormonal contraception. As observed in men, T administration to these monkeys induced azoospermia in some animals and variable degrees of spermatogenic suppression in others. Based on their sperm counts, we divided these animals into two groups: azoospermic (azoo; n = 4) and nonazoospermic (nonazoo; n = 5) groups. Sperm density, testis volumes, and serum T, bioassayable LH (bioLH), immunoassayable FSH (immunoFSH), bioassayable FSH (bioFSH), and inhibin B were examined every 2 wk during the control period, 20 wk of T administration using SILASTIC brand (Dow Corning Corp.) implants, and recovery. Testes were biopsied for estimation of intratesticular T, dihydrotestosterone, and 5alpha-androstane-3alpha,17beta-diol. Serum T levels increased 1.5- to 2-fold, leading to decreased bioLH levels (48% of control) and intratesticular T levels (15% of control); neither LH nor intratesticular T levels differed between the azoo and nonazoo groups. In contrast, serum levels of FSH, by both bio- and immunoassay, during T administration were significantly lower in the azoo than in the nonazoo group. These results suggest that the degree of suppression of spermatogenesis is closely related to the degree of suppression of FSH levels and not to the levels of intratesticular androgens or to serum LH. These results imply that FSH plays a key role in supporting spermatogenesis in monkeys in this experimental regimen and suggest that maximal suppression of FSH may be essential to ensure consistent azoospermia in men during hormonal contraception.

Androgens↗

Hormonal changes in the menopause transition.

The menopause is the permanent cessation of menstruation resulting from the loss of ovarian follicular activity. It is heralded by the menopausal transition, a period when the endocrine, biological, and clinical features of approaching menopause begin. A common initial marker is the onset of menstrual irregularity. The biology underlying the transition to menopause includes central neuroendocrine changes as well as changes within the ovary, the most striking of which is a profound decline in follicle numbers. Follicle-stimulating hormone (FSH) is an established indirect marker of follicular activity. In studies of groups of women, its concentration, particularly in the early follicular phase of the menstrual cycle, begins to increase some years before there are any clinical indications of approaching menopause. The rise in FSH is the result of declining levels of inhibin B (INH-B), a dimeric protein that reflects the fall in ovarian follicle numbers, with or without any change in the ability of the lining granulosa cells to secrete INH-B. Estradiol levels remain relatively unchanged or tend to rise with age until the onset of the transition and are usually well preserved until the late perimenopause, presumably in response to the elevated FSH levels. During the transition, hormone levels frequently vary markedly - hence, measures of FSH and estradiol are unreliable guides to menopausal status. Concentrations of testosterone have been reported to fall by about 50% during reproductive life, between the ages of 20 and 40. They change little during the transition and, after menopause, may even rise. Dehydroepiandrosterone (DHEA) and DHEAS, its sulphate, on the other hand, decline with age, without any specific influence of the menopause. Symptoms of the menopause can be interpreted as resulting primarily from the profound fall in estradiol, occurring over a 3- to 4-year period around final menses, a fall that presumably contributes importantly to the beginning, in the late perimenopause, of loss of bone mineral density.

Adult↗

The relationship between the endocrine characteristics and the regularity of menstrual cycles in the approach to menopause.

OBJECTIVE: There is currently little longitudinal data available on the serum hormonal characteristics of the menstrual cycles observed in women as they approach their final menstrual period (FMP) or menopause. We sought to determine whether the onset of irregular menses, marking the menopause transition, signifies the occurrence of anovulatory, potentially infertile cycles. DESIGN: We studied 12 subjects, initially aged 45 to 47 years, who provided daily menstrual diaries, and had blood samples collected annually, three times weekly for 4 consecutive weeks, over a period of 36 to 98 months until FMP, for measurements of serum follicle-stimulating hormone (FSH), luteinizing hormone, estradiol, and progesterone. The definition of entry into the early menopause transition was the occurrence of more than two cycles, in any consecutive sequence of 10, where cycle length was less than 23 or more than 35 days. Entry into the late transition was determined from the first observation of either 60-day or 90-day amenorrhea. Cycles were characterized endocrinologically as normal ovulatory, abnormal luteal phase, and anovulatory with evidence of ovarian follicular activity. RESULTS: The early transition had an average duration of 47 months from onset until FMP. Ten of the 12 subjects had one or more ovulatory cycles during the transition. Anovulatory cycles with ovarian activity were noted in 9 of the 12 subjects, only after entry into early and/or late transition. CONCLUSIONS: Ovulatory cycles occurred both before and after entry into the early and/or late menopause transition in subjects older than 45 years of age, whereas anovulatory cycles were observed only during the transition. The ovulatory cycles were generally associated with normal menses, whereas anovulatory cycles showed long duration and/or abnormal bleeding patterns. The occurrence of cycle irregularity is associated with an increasing frequency of anovulatory cycles, which herald the occurrence of FMP. No conclusion could be drawn regarding the appropriate definition of entry into the late transition. The definition adopted for entry into the early transition merits further validation.

Anovulation↗