Postmenopausal hyperthecosis: Functional dysregulation of androgenesis in climacteric ovary

Magee-Womens Hospital, Pittsburgh, Pennsylvania, United States
Obstetrics and Gynecology (Impact Factor: 4.37). 06/2002; 99(5 Pt 2):893-7. DOI: 10.1016/S0029-7844(01)01588-5
Source: PubMed

ABSTRACT Hyperandrogenism of ovarian origin is rare in postmenopausal women. However, there is evidence that the ovaries of postmenopausal women are active endocrine glands, secreting mainly androgens.
A postmenopausal woman sought treatment for progressive hirsutism. Endocrine evaluation revealed androgen excess. Transvaginal ultrasound revealed enlarged ovaries. Hysterectomy and bilateral oophorectomy were recommended. However, surgery had to be withheld for 6 months while the patient recovered from an acute myocardial infarction. In the interim, the patient's hyperandrogenemia was successfully treated with monthly injections of the gonadotropin-releasing hormone agonist (GnRH), leuprolide acetate.
This report illustrates the potential for postmenopausal ovaries to become active androgen-secreting endocrine organs. It also demonstrates the efficacy of pharmacologic intervention for postmenopausal ovarian hyperthecosis when the patient is a poor surgical candidate.

Download full-text


Available from: Esther Krug, Aug 31, 2015
1 Follower
  • Source
    • "In the menopausal ovary, follicles undergo atresia, with sparing of androgen-producing theca –interstitial cell components (Shifren and Schiff, 2000). Post-menopausal ovaries are smaller and consist primarily of stromal cells, which retain receptors for LH (Foth and Romer, 2001), that could respond to its rise in circulation secreting testosterone but produce little estrogen (Longcope, 2001; Krug and Berga, 2002). Advancing age coupled with estrogen loss and hyperandrogenemia could lead to insulin resistance, increasing the risks of type II diabetes, hyperlipidemia and cardiovascular disease. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Genetically modified follitrophin receptor knockout female mice with total FSH-receptor (FSH-R) deletion are sterile and their combined estrogen deficiency-hyperandrogenemic status provides an experimental paradigm to study the effect of hormonal imbalances on ovarian function and metabolic alterations. Elevated LH levels causing hyperandrogenemia perturb normal folliculogenesis. To control diverse pathophysiology associated with hormonal imbalances, we investigated the effects of transplanting a single normal mouse ovary in young mutants. An intact FSH-R signalling system in the graft responded promptly to the up-regulated pituitary gonadotrophins circulating in the host mutant. Resumption of regular estrous cycles validated stimulation of uterine functions. Secretions from the viable functioning grafts partially corrected follicular abnormalities originally present in host ovaries. Stromal hyperplasia responsible for high ovarian LH-receptor and key enzymes in host thecal/interstitial complex and hyperandrogenemia was reduced in host ovaries. Increases in plasma estradiol and reduced LH and free testosterone re-established the negative-feedback system. Reduced android obesity and activation of mammary glands indicated the combined beneficial effects of normalized steroid hormones on target organs. These data provide evidence that ovarian transplantation in mutants corrects estrogen loss and hyperandrogenemia. However, correction of hormonal imbalances is not sufficient to fully restore effects of FSH-R loss in host granulosa cells.
    Molecular Human Reproduction 06/2007; 13(5):287-97. DOI:10.1093/molehr/gam008 · 3.48 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease is the leading cause of death in women and claims the lives of more than half a million women every year. Hypertension is one of the most prevalent and powerful contributors to atherosclerotic cardiovascular disease. Hypertension affects more men than women until 55 years of age, but after age 55, the percentage of women is higher. Estrogen deficiency has been linked to the rapid increase in cardiovascular disease in women who have undergone natural or surgical menopause. Hormone replacement therapy (HRT) has been shown to decrease the incidence of cardiovascular disease and, in some studies, to reduce blood pressure in postmenopausal women. However, little information is available on the effects of HRT on blood pressure in hypertensive postmenopausal patients. The cardioprotective effects of estrogens are not completely understood but may involve direct effects on blood vessels through modulation of endogenous vasoconstrictors and vasodilators and through reductions in serum lipoprotein and cholesterol levels. Experimental evidence suggests that estrogen increases the biological actions of nitric oxide and decreases the actions of angiotensin. After menopause, loss of the vascular protective effects of estrogens may unmask a population of women particularly prone to hypertension who would be at higher risk for cardiovascular disease.
    Current Hypertension Reports 05/2000; 2(2):202-7. DOI:10.1007/s11906-000-0083-2 · 3.90 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Blood pressure increases in many women after menopause. Hypertension is one of the major risk factors for cardiovascular disease. However, the mechanisms responsible for the postmenopausal increase in blood pressure are yet to be elucidated. Various humoral systems have been proposed to play a role in postmenopausal hypertension, such as changes in estrogen/androgen ratios, increases in endothelin and oxidative stress, and activation of the renin-angiotensin system (RAS). In addition, obesity, type II diabetes, and activation of the sympathetic nervous system are common in postmenopausal women and may also play important roles. However, progress in elucidating the mechanisms responsible for postmenopausal hypertension has been hampered by the lack of a suitable animal model. The aging female spontaneously hypertensive rat (SHR) exhibits many of the characteristics found in postmenopausal women. In this review, some of the possible mechanisms that could play a role in postmenopausal hypertension are discussed, as well as the characteristics of the aged female SHR as a model to study.
    Hypertension 06/2004; 43(5):918-23. DOI:10.1161/01.HYP.0000124670.03674.15 · 7.63 Impact Factor
Show more