The effects of long-term androgen treatment on the ovary

Amirikia, Hassan; Savoy‐Moore, Ruth T.; Sundareson, Alistair S.; Moghissi, Kamran S.

doi:10.1016/s0015-0282(16)49155-7

Cited by 58 publications

(35 citation statements)

References 15 publications

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“…The low gonadotropin levels and menstrual irregularities observed in Cushing's syndrome do not appear to be the result of elevated serum androgen levels, an observation in agreement with the belief that androgens do not play a major role in the neuroendocrine regulation of the menstrual cycle (49,50). Also, testosterone administration to female to male transsexuals induces morphological features of polycystic ovarian disease (51,52). However, these alterations have only been produced when serum levels of testosterone are elevated, higher than the levels encountered in normal males, females with virilizing tumors, or the patients studied here (53)(54)(55)(56).…”

Section: Discussionsupporting

confidence: 75%

Menstrual Abnormalities in Women with Cushing’s Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels

Lado-Abeal

Rodriguez-Arnao

Newell‐Price

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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Menstrual irregularity is a common complaint at presentation in women with Cushing's syndrome, although the etiology has been little studied. We have assessed 45 female patients (median age, 32 yr; range, 16 -41 yr) with newly diagnosed pituitary-dependent Cushing's syndrome. Patients were subdivided into 4 groups according to the duration of their menstrual cycle: normal cycles (NC; 26 -30 days), oligomenorrhea (OL; 31-120 days), amenorrhea (AM; Ͼ120 days), and polymenorrhea (PM; Ͻ26 days). Blood was taken at 0900 h for measurement of LH, FSH, PRL, testosterone, androstenedione, dehydroepiandrosterone sulfate, estradiol (E 2 ), sex hormone-binding globulin (SHBG), and ACTH; cortisol was sampled at 0900, 1800, and 2400 h. The LH and FSH responses to 100 g GnRH were analyzed in 23 patients. Statistical analysis was performed using the nonparametric Mann-Whitney U and Spearman tests.Only 9 patients had NC (20%), 14 had OL (31.1%), 15 had AM (33.3%), and 4 had PM (8.8%), whereas 3 had variable cycles (6.7%). By group, AM patients had lower serum E 2 levels (median, 110 pmol/L) than OL patients (225 pmol/L; P Ͻ 0.05) or NC patients (279 pmol/L; P Ͻ 0.05), and higher serum cortisol levels at 0900 h (800 vs.602 and 580 nmol/L, respectively; P Ͻ 0.05) and 1800 h (816 vs. 557 and 523 nmol/L, respectively; P Ͻ 0.05) and higher mean values from 6 samples obtained through the day (753 vs. 491 and 459 nmol/L, respectively; P Ͻ 0.05). For the whole group of patients there was a negative correlation between serum E 2 and cortisol at 0900 h (r ϭ Ϫ0.50; P Ͻ 0.01) and 1800 h (r ϭ Ϫ0.56; P Ͻ 0.01) and with mean cortisol (r ϭ Ϫ0.46; P Ͻ 0.05). No significant correlation was found between any serum androgen and E 2 or cortisol. The LH response to GnRH was normal in 43.5% of the patients, exaggerated in 52.1%, and decreased in 4.4%, but there were no significant differences among the menstrual groups. No differences were found in any other parameter.In summary, in our study 80% of patients with Cushing's syndrome had menstrual irregularity, and this was most closely related to serum cortisol rather than to circulating androgens. Patients with AM had higher levels of cortisol and lower levels of E 2 , while the GnRH response was either normal or exaggerated. Our data suggest that the menstrual irregularity in Cushing's disease appears to be the result of hypercortisolemic inhibition of gonadotropin release acting at a hypothalamic level, rather than raised circulating androgen levels. (J Clin Endocrinol Metab 83: 3083-3088, 1998)

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Section: Discussionsupporting

confidence: 75%

Menstrual Abnormalities in Women with Cushing’s Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels

Lado-Abeal

Rodriguez-Arnao

Newell‐Price

et al. 1998

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…In human studies, increases in the numbers of atretic follicles were observed in the ovaries of androgen-administrated FTM persons [3,8,9]. The treatment periods were fairly long, averaging 38 months [3], 21 months [8] and 35 months [9], respectively. Consistent with those reports, we observed increases in the numbers of atretic follicles with long-term DHEA treatment.…”

Section: Discussionmentioning

confidence: 99%

“…In another study, reproductive-age rhesus monkeys receiving high doses of androgen in the short-term were equally as likely to exhibit an increase in small follicles as monkeys receiving low doses over a longer term [5]. In addition, examination of the histology of ovaries in androgen-administered FTM patients revealed increased follicular atresia, though the morphogenesis of polycystic ovaries is controversial [3,8,9]. Judging from these findings, it appears that androgen administration may impact folliculogenesis and subsequent ovarian morphology, leading to the development of the PCO morphology, but the effects of exogenous androgens on ovarian morphology may vary depending on the period and duration of the androgen administration and the amount of hormone administered.…”

Section: Introductionmentioning

confidence: 99%

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

et al. 2014

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BackgroundHyperandrogenism is the primary manifestation of polycystic ovary syndrome (PCOS), which appears to be caused by excess exposure to androgen. As such, androgenized animal models have been developed and investigated to study the etiology of PCOS. Anti-Mullerian hormone (AMH) is known to be associated with follicle growth, and its levels are two to three times higher in women with PCOS than in those with normal ovaries. We studied how duration of androgen administration affects folliculogenesis and AMH expression.MethodsWe divided 30 immature (3-week-old) Sprague Dawley rats into six groups. Three groups were injected each evening with dehydroepiandrosterone (DHEA) (6 mg/100 g body weight/0.2 ml sesame oil) for 7, 15 or 30 days, respectively. The three control groups were injected with 0.2 ml of sesame oil for the corresponding lengths of time. Resected ovaries were sectioned and examined to determine follicle numbers at each developmental stage, and immunostained to assess AMH expression.ResultsOn day 7, follicle numbers and AMH expression levels at each developmental stage of follicle growth were similar in the respective control and DHEA groups. On day 15, the total follicle number (P = 0.041), the percentage of primordial follicles (P = 0.039) and AMH expression were significantly greater in the DHEA than the control group. On day 30, the percentages of primordial (P = 0.005), primary (P = 0.0002) and atretic (P = 0.03) follicles were significantly greater in the DHEA group, whereas the percentage of intermediary follicles (early pre-antral, late preantral, and early antral follicles) was significantly lower in the DHEA group (P = <0.0001). AMH expression in DHEA-treated rats on day 30 was seen exclusively in the primordial (P = 0.0413) and late antral follicles (p = 0.028).ConclusionsAndrogen administration increases AMH production in a process that regulates the growth of primordial follicles. That is, androgen-induced AMH expression provides local negative feedback to folliculogenesis augmented by androgen.

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“…It is possible that DHEA treatment may create PCO like characteristics in the aging ovary. Long term exogenous androgen exposure can induce PCO like histological and sonographic changes [27,28]. Androgens have been reported to suppress apoptosis [29,30].…”

Section: Discussionmentioning

confidence: 99%

Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function

Barad

Brill

Gleicher

2007

J Assist Reprod Genet

184

168

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The effects of long-term androgen treatment on the ovary

Cited by 58 publications

References 15 publications

Menstrual Abnormalities in Women with Cushing’s Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels

Menstrual Abnormalities in Women with Cushing’s Disease Are Correlated with Hypercortisolemia Rather Than Raised Circulating Androgen Levels

Long-term treatment with dehydroepiandrosterone may lead to follicular atresia through interaction with anti-Mullerian hormone

Update on the use of dehydroepiandrosterone supplementation among women with diminished ovarian function

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