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Female age has been known to define reproductive outcome since antiquity; attempts to improve ovarian function may be considered against a sociocultural landscape that foreshadows current practice. Ancient writs heralded the unlikely event of an older woman conceiving as nothing less than miraculous. Always deeply personal and sometimes dynastically pivotal, the goal of achieving pregnancy often engaged elite healers or revered clerics for help. The sorrow of defeat became a potent motif of barrenness or miscarriage lamented in art, music, and literature. Less well known is that rejuvenation practices from the 1900s were not confined to gynecology, as older men also eagerly pursued methods to turn back their biological clock. This interest coalesced within the nascent field of endocrinology, then an emerging specialty. The modern era of molecular science is now offering proof-of-concept evidence to address the once intractable problem of low or absent ovarian reserve. Yet, ovarian rejuvenation by platelet-rich plasma (PRP) originates from a heritage shared with both hormone replacement therapy (HRT) and sex reassignment surgery. These therapeutic ancestors later developed into allied, but now distinct, clinical fields. Here, current iterations of intraovarian PRP are discussed with historical and cultural precursors centering on cell and tissue regenerative effects. Intraovarian PRP thus shows promise for women in menopause as an alternative to conventional HRT, and to those seeking pregnancy—either with advanced reproductive technologies or as unassisted conceptions.
Cellular senescence is characterized by a degenerative process accompanied by poor tissue homeostasis and decline of organ function [1]. In clinical infertility practice, the ovaries generally are the first to suffer age impairment over time. Traditional teaching still embraces the basic tenet that females have a limited, non-replenishable oocyte endowment present at birth, which declines during adulthood and is eventually lost at menopause [2]. The basic concept of rejuvenation is not new, remaining topical yet contested. As currently offered, ovarian rejuvenation descends from a long line of medical efforts of varied efficacy that gained notoriety more than a century ago. In the public consciousness, any discussion of rejuvenation might have gained less notice had it not been for the developing study of gonadal physiology. Parallel improvements in surgical techniques also made human ovary tissue grafts workable from the late 1800′s, and testicular transplants for farm animals had been described even earlier [3]. Against this background, the mystique of ‘sex gland’ modulation was ideal for showcasing via the nascent clinical field of endocrinology.
It is now more accepted that human ovarian stem cells might persist into adulthood, retaining a capacity to differentiate into competent oocytes under appropriate conditions [4]. While no consensus exists regarding the exact signaling milieu necessary to elicit this replenishment, recent work suggests that pluripotency, self-renewal, and diminished follicular reserve in old age all may be subject to modulation [4, 5]. This approach impacts reproductive medicine practice and patient counseling, as older ovaries not only supply fewer eggs but also yield cells of reduced competency—chiefly due to ploidy error. Moreover, the cumulative effect of age-sensitive mutations generally accelerates the exhaustion of ovarian reserve as reflected by diminished serum AMH and primordial follicle number [1, 5, 6]. When intraovarian PRP was administered to patients not seeking pregnancy [7], this non-pharmaceutical approach improved quality of life at least as effectively as standard hormone replacement therapy (HRT).
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Near the end of his life, novelist Thomas Mann (1875–1955) was among the first to portray gynecology with accuracy in popular literature. His short story, The Black Swan, describes a 50yr old widow yearning for recaptured youth. When menopause does reverse, her hopeful wish of rejuvenation seems granted. A heightened state of sexual arousal is perceived, where vitality and libido had previously withered. But her river of time did not really run backward. Instead, the high estrogen state was a symptom of advancing ovarian cancer. Death soon followed and the cruelty of nature’s hoax is revealed post-mortem [8].
William Butler Yeats (1865–1939) likewise had navigated his own creative drift and listlessness even earlier. At age 69, the Nobel laureate underwent an odd quasi-vasectomy seeking renewal. Praising that surgery, Yeats later acknowledged his recharged energy and sexual drive. That verve did not pass unnoticed in Dublin society, where he became known as the ‘gland old man’ [9]. Yeats’ literary output certainly charts an impressive post-operative flourish of late poems, which now rank among his most acclaimed works.
Not every man enjoyed such dramatic results. Sigmund Freud (1856–1939), who at age 67 had the same operation, obtained no impact on productivity. His quest for rejuvenation emerged concurrently with an awful struggle with oral cancer, entailing multiple painful surgical revisions. It was Freud’s belief that this vasectomy-variant might assuage his cancer, although he later admitted that ‘rejuvenation’ accomplished nothing [10]. Many less famous older men underwent this surgery in the early 20th century, in search of both mental and physical rejuvenation.
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But what surgery was done? And why exactly was it thought so worthwhile? The concept that a type of vasectomy could yield such results traces back to the Vienna Academy and Prof. Eugen Steinach (1861–1944). What Steinach provided was a modification to standard sterilization, a familiar operation first reported in 1899 [9]. His hemi-vasectomy, now discredited, cut only one structure and conferred no contraceptive benefit. The belief was that this unilateral snip would shift the work of the affected testicle away from sperm production, and towards full-time production of male sex hormones. Steinach’s papers were widely accepted as key contributions to the discipline of the ‘science of fatigue’ [9]. Terminology eventually trapped the teacher; gentlemen did not merely have Dr. Steinach’s operation—they were ‘Steinached’ [10]. Tragically for women’s health of the day, ovarian X-ray treatment was considered the equivalent female procedure for what Prof. Steinach was doing for men in Vienna [10].
In 1930, Alice of Battenberg (1885–1969) a great-granddaughter of Queen Victoria, was suffering from chronic schizophrenia and arrived at Berlin’s Tegel Castle Sanatorium—the world’s first psychiatric clinic. A quiet childhood in Greece was upset by the turbulence of war and coup d’état, necessitating her family’s exile. There is no record that she had become distraught with menopause in her mid-40s, yet the clinic director sought the opinion of Freud who suggested ovarian X-ray therapy. This recommendation would have aligned with accepted techniques well known to Freud himself [11]. Of course, X-rays administered to the pelvis did nothing but increase medical problems for Princess Alice. The harms of ionizing radiation are now better understood in the post-nuclear age, especially cell death and endocrine collapse. Recent animal research commissioned to assess health risks for future female astronauts [12] has verified serious ovarian injury can occur even at trace radiation doses.
Another case is the California author Gertrude Atherton (1857–1948). She penned Black Oxen as a semi-autobiographical work, telling of an aging woman regaining youth with ‘glandular therapy’. While operative records are missing for contemporary critique, at age 66 Atherton did have some kind of experimental surgery and was convinced that rejuvenation had positive results for her [10].
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After his death, Prof. Steinach slipped into obscurity despite having received multiple nominations for the Nobel Prize [13]. It became difficult to fit the topic of rejuvenation in the clinical canon, yet contemporary diarists recount him as a caring professional and dedicated researcher. Working ahead of then-accepted norms, his energies were focused on how best to integrate findings from highly innovative animal experiments into regular clinical practice [10]. Specifically, Steinach’s theories were among the first to posit how reproductive capacity and sexual phenotype could be changed if given proper ‘glandular’ inducements [9]. This offered crucial support to a new physiology of chemical/steroid regulation, eclipsing the old physiology centered on nervous system regulation [13].
Little persuasion was needed to show that if rats castrated before puberty could get back their vigor when given proper signals, then this same goal might also be possible for humans of a certain age. In the early 20th century, the door was thus open for uncritical belief in rejuvenation—and Steinach did not disappoint. He recorded how
But what surgery was done? And why exactly was it thought so worthwhile? The concept that a type of vasectomy could yield such results traces back to the Vienna Academy and Prof. Eugen Steinach (1861–1944). What Steinach provided was a modification to standard sterilization, a familiar operation first reported in 1899 [9]. His hemi-vasectomy, now discredited, cut only one structure and conferred no contraceptive benefit. The belief was that this unilateral snip would shift the work of the affected testicle away from sperm production, and towards full-time production of male sex hormones. Steinach’s papers were widely accepted as key contributions to the discipline of the ‘science of fatigue’ [9]. Terminology eventually trapped the teacher; gentlemen did not merely have Dr. Steinach’s operation—they were ‘Steinached’ [10]. Tragically for women’s health of the day, ovarian X-ray treatment was considered the equivalent female procedure for what Prof. Steinach was doing for men in Vienna [10].
In 1930, Alice of Battenberg (1885–1969) a great-granddaughter of Queen Victoria, was suffering from chronic schizophrenia and arrived at Berlin’s Tegel Castle Sanatorium—the world’s first psychiatric clinic. A quiet childhood in Greece was upset by the turbulence of war and coup d’état, necessitating her family’s exile. There is no record that she had become distraught with menopause in her mid-40s, yet the clinic director sought the opinion of Freud who suggested ovarian X-ray therapy. This recommendation would have aligned with accepted techniques well known to Freud himself [11]. Of course, X-rays administered to the pelvis did nothing but increase medical problems for Princess Alice. The harms of ionizing radiation are now better understood in the post-nuclear age, especially cell death and endocrine collapse. Recent animal research commissioned to assess health risks for future female astronauts [12] has verified serious ovarian injury can occur even at trace radiation doses.
Another case is the California author Gertrude Atherton (1857–1948). She penned Black Oxen as a semi-autobiographical work, telling of an aging woman regaining youth with ‘glandular therapy’. While operative records are missing for contemporary critique, at age 66 Atherton did have some kind of experimental surgery and was convinced that rejuvenation had positive results for her [10].
Blood To Brain Communication In Aging And Rejuvenation
After his death, Prof. Steinach slipped into obscurity despite having received multiple nominations for the Nobel Prize [13]. It became difficult to fit the topic of rejuvenation in the clinical canon, yet contemporary diarists recount him as a caring professional and dedicated researcher. Working ahead of then-accepted norms, his energies were focused on how best to integrate findings from highly innovative animal experiments into regular clinical practice [10]. Specifically, Steinach’s theories were among the first to posit how reproductive capacity and sexual phenotype could be changed if given proper ‘glandular’ inducements [9]. This offered crucial support to a new physiology of chemical/steroid regulation, eclipsing the old physiology centered on nervous system regulation [13].
Little persuasion was needed to show that if rats castrated before puberty could get back their vigor when given proper signals, then this same goal might also be possible for humans of a certain age. In the early 20th century, the door was thus open for uncritical belief in rejuvenation—and Steinach did not disappoint. He recorded how
