Ovarian Androgen Production in Postmenopausal Women

Fogle, R.H.; Stanczyk, Frank Z.; Zhang, Xiaohua; Paulson, Richard J.

doi:10.1210/jc.2007-0581

Cited by 249 publications

(131 citation statements)

References 22 publications

Supporting

Mentioning

108

Contrasting

Unclassified

Order By: Relevance

“…Sixty percent of testosterone in premenopausal women originates from ovarian sources, whereas 40% is derived from adrenal precursors. Interestingly, this division changes little with the menopause, with about 50% of testosterone levels continuing to be derived from ovarian sources [53][54][55]. Therefore, processes, diseases and medications that affect ovarian and/or adrenal function may affect testosterone levels in pre-or post-menopausal women and may cause androgen deficiency in women.…”

Section: Effects Of Androgen Deficiency and Testosterone Administratimentioning

confidence: 99%

Androgen deficiency: effects on body composition

Miller

2008

Pituitary

View full text Add to dashboard Cite

Published data on the effects of androgen deficiency and testosterone administration on body composition in men and women are reviewed. In experimental paradigms, androgen deprivation decreases lean body mass and increases fat mass in men, and physiologic replacement reverses these abnormalities. The anabolic effects of testosterone administration on muscle in men are well-established, and current understanding of the underlying mechanisms are discussed. Randomized, placebo-controlled studies have been performed to investigate the effects of testosterone administration on body composition in a number of male hypogonadal states, including HIV-associated weight loss, supraphysiologic glucocorticoid administration, aging and obesity, with variable outcomes, and the results are reviewed. There are few data investigating the effects of hypoandrogenemia or androgen replacement on body composition in women, in whom endogenous testosterone levels are a fraction of those in men. A recent randomized, placebo-controlled study of physiologic testosterone replacement therapy in women with profound hypoandrogenemia due to hypopituitarism demonstrated an increase in skeletal muscle mass but no change in body fat. Further research is needed to establish the effects of endogenous androgens on the regulation of body composition in women.

show abstract

Section: Effects Of Androgen Deficiency and Testosterone Administratimentioning

confidence: 99%

Androgen deficiency: effects on body composition

Miller

2008

Pituitary

View full text Add to dashboard Cite

show abstract

“…The ovary is an important source of testosterone and other androgens in postmenopausal women (Fogle et al 2007). Synthesis takes place in the stromal tissue under the stimulus of the gonadotropin luteinizing hormone (LH) (Adashi 1994, Laughlin et al 2000.…”

Section: The Postmenopausal Ovary As Source Of Excessive Testosteronementioning

confidence: 99%

“…Adashi 1994, Sluijmer et al 1998, Laughlin et al 2000, Burger 2002, Jongen et al 2003, Fogle et al 2007) which can be corrected by oophorectomy (Adashi 1994, Sluijmer et al 1998, Laughlin et al 2000, Jongen et al 2003, Fogle et al 2007, Kotsopoulos et al 2012. In a study of BRCA1 and BRCA2 mutation carriers, Kotsopoulos et al (2012) observed a significant decrease in the risk of breast cancer in women who are oophorectomized after menopause than that in women in natural menopause and suggested that the reduction of circulating testosterone levels after oophorectomy might account for its protective effect.…”

Section: :11mentioning

confidence: 99%

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy

Muti

Sant

Meneghini

2017

Endocrine-Related Cancer

View full text Add to dashboard Cite

Five years of adjuvant therapy with anti-estrogens reduce the incidence of disease progression by about 50% in estrogen receptor-positive breast cancer patients, but late relapse can still occur after anti-estrogens have been discontinued. In these patients, excessive androgen production may account for renewed excessive estrogen formation and increased risks of late relapse. In the 50% of patients who do not benefit with anti-estrogens, the effect of therapy is limited by de novo or acquired resistance to treatment. Androgen receptor and epidermal growth factor receptor overexpression are recognized mechanisms of endocrine resistance suggesting the involvement of androgens as activators of the androgen receptor pathway and as stimulators of epidermal growth factor synthesis and function. Data from a series of prospective studies on operable breast cancer patients, showing high serum testosterone levels are associated to increased risk of recurrence, provide further support to a role for androgens in breast cancer progression. According to the above reported evidence, we proposed to counteract excessive androgen production in the adjuvant setting of estrogen receptorpositive patients and suggested selecting postmenopausal patients with elevated levels of serum testosterone, marker of ovarian hyperandrogenemia, for adjuvant treatment with a gonadotropins-releasing hormone analogue (medical oophorectomy) in addition to standard therapy with anti-estrogens. The proposed approach provides an attempt of personalized medicine that needs to be further investigated in clinical trials.

show abstract

“…All androgens in postmenopausal women are suggested to be made locally in peripheral target tissues according to the mechanism of local intracrine formation of steroids. The contribution of ovarian production of circulating androgenic precursors and thus potentially supporting this local intracrine metabolism of steroids is underlined by studies showing serum dehydroepiandrosterone (DHEA); the inactive precursor hormone of androgens is higher in intact compared with oophorectomized women (Labrie et al 2011, Labrie 2015, and several studies reported that the serum levels of androgens between ovarian and peripheral veins were significantly different between early and late menopausal women, suggesting that the production of androgens by the ovaries could persist even 10 years after the onset of menopause, but may subsequently decline (Fogle et al 2007, Maruoka et al 2014. Therefore, the degree and duration to which postmenopausal ovaries remain a viable androgen-producing organ is still controversial and not fully understood.…”

Section: Serum Androgen and Increased Risk Of Developing Endometrial mentioning

confidence: 99%

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Itō¹,

Miki²,

Suzuki³

et al. 2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

In situ estrogen biosynthesis is considered to play pivotal roles in the development and progression of human endometrial carcinoma. However, the biological roles of androgen have remained virtually unknown. Various epidemiological studies have revealed that elevated serum androgen levels are generally associated with an increased risk of developing endometrial carcinoma; however, studies directly examining androgens in carcinoma tissues are relatively rare and reviews summarizing this information are scarce. Therefore, we summarized recent studies on androgens in endometrial carcinoma, especially focusing androgen actions and in situ androgen biosynthesis. Among the enzymes required for local biosynthesis of androgen, 17β-hydroxysteroid dehydrogenase type 5 (conversion from androstenedione to testosterone) and 5α-reductase (reduction of testosterone to dihydrotestosterone (DHT)) are the principal enzymes involved in the formation of biologically most potent androgen, DHT. Both enzymes and androgen receptor were expressed in endometrial carcinoma tissues, and in situ production of DHT has been reported to exist in endometrial carcinoma tissues. However, testosterone is not only a precursor of DHT production, but also a precursor of estradiol synthesis, as a substrate of the aromatase enzyme. Therefore, aromatase could be another key enzyme serving as a negative regulator for in situ production of DHT by reducing amounts of the precursor. In an in vitro study, DHT was reported to exert antiproliferative effects on endometrial carcinoma cells. Intracrine mechanisms of androgens, the downstream signals of AR, which are directly related to anticancer progression, and the clinical significance of DHT-AR pathway in the patients with endometrial carcinoma have, however, not been fully elucidated.

show abstract

Ovarian Androgen Production in Postmenopausal Women

Abstract: The postmenopausal ovary is hormonally active, contributing significantly to the circulating pool of T. Furthermore, this contribution appears to persist in women as long as 10 yr beyond the menopause.

Cited by 249 publications

References 22 publications

Androgen deficiency: effects on body composition

Androgen deficiency: effects on body composition

Medical ovariectomy in menopausal breast cancer patients with high testosterone levels: a further step toward tailored therapy

In situ androgen and estrogen biosynthesis in endometrial cancer: focus on androgen actions and intratumoral production

Contact Info

Product

Resources

About